Summary
Critically ill patients exhibit a range of organ dysfunctions and often require treatment with a variety of drugs including sedatives, analgesics, neuromuscular blockers, antimicrobials, inotropes and gastric acid suppressants. Understanding how organ dysfunction can alter the pharmacokinetics of drugs is a vital aspect of therapy in this patient group. Many drugs will need to be given intravenously because of gastrointestinal failure. For those occasions on which the oral route is possible, bioavailability may be altered by hypomotility, changes in gastrointestinal pH and enteral feeding. Hepatic and renal dysfunction are the primary determinants of drug clearance, and hence of steady-state drug concentrations, and of efficacy and toxicity in the individual patient.
Oxidative metabolism is the main clearance mechanism for many drugs and there is increasing recognition of the importance of decreased activity of the hepatic cytochrome P450 system in critically ill patients. Renal failure is equally important with both filtration and secretion clearance mechanisms being required for the removal of parent drugs and their active metabolites. Changes in the steady-state volume of distribution are often secondary to renal failure and may lower the effective drug concentrations in the body. Failure of the central nervous system, muscle, the endothelial system and endocrine system may also affect the pharmacokinetics of specific drugs. Time-dependency of alterations in pharmacokinetic parameters is well documented for some drugs. Understanding the underlying pathophysiology in the critically ill and applying pharmacokinetic principles in selection of drug and dose regimen is, therefore, crucial to optimising the pharmacodynamic response and outcome.
Article PDF
Similar content being viewed by others
References
Mann HJ, Fuhs DW, Cerra FB. Pharmacokinetics and pharmacodynamics in critically ill patients. World J Surg 1987; 11: 210–7.
Fuhs DW, Mann HJ, Kubajak CA, et al. Intrapatient variation of aminoglycoside pharmacokinetics in critically ill surgery patients. Clin Pharm 1988; 7: 207–13.
Jellett LB, Heazlewood VJ. Pharmacokinetics in acute illness. Med J Aust 1990; 153: 534–41.
Zielmann S, Mielck F, Kahl R, et al. A rational basis for the measurement of free phenytoin concentration in critically ill trauma patients. Ther Drug Monit 1994; 16: 139–44.
Park GR. Molecular mechanisms of drug metabolism in the critically ill. Br J Anaesth 1996; 77: 32–49.
Hawker F. The critically ill patient with abnormal liver function tests. In: Park GR, editor. The liver. London: WB Saunders Co Ltd, 1993: 286–323.
Park GR, Miller E. What changes drug metabolism in critically ill patients. III: effect of pre-existing disease on the metabolism of midazolam. Anaesthesia 1996; 51: 431–4.
Park GR, Miller E, Navapurkar V. What changes drug metabolism in critically ill patients. II: serum inhibits the metabolism of midazolam in human hepatocytes. Anaesthesia 1996; 51: 11–5.
Park GR, Pichard L, Tinel M, et al. What changes drug metabolism in critically ill patients: two preliminary studies in isolated human hepatocytes. Anaesthesia 1994; 49: 188–91.
Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolise midazolam. Anaesthesia 1987; 42: 619–26.
Muller CM, Scierka A, Stiller RL, et al. Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin. Anesthesiology 1996; 84: 1435–42.
Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes [review]. Ann Pharmacother 1995; 29: 619–24.
Kerremans AL. Cytochrome P450 isoenzymes: importance for the internist [review]. Neth J Med 1996; 48: 237–43.
Macnab MS, Macrae DJ, Guy E, et al. Profound reduction in morphine clearance and liver blood flow in shock. Intens Care Med 1986; 12: 366–9.
Bower S, Sear JW, Roy RC, et al. Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients. Br J Anaesth 1992; 68: 462–5.
Bodenham A, Shelly MP, Park GR. The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients. Clin Pharmacokinet 1988; 14: 347–73.
Russell WJ, Frewin DB, Jonsson JR. Pulmonary extraction of catecholamines in critically ill patients. Anaesth Intens Care 1982; 10: 319–23.
Watling SM, Dasta JF. Aminoglycoside dosing considerations in intensive care unit patients. Ann Pharmacother 1993; 27: 351–7.
Martin C, Lambert D, Bruguerolle B, et al. Ofloxacin pharmacokinetics in mechanically ventilated patients. Antimicrob Agents Chemother 1991; 35: 1582–5.
Golper TA, Vincent HH, Kroh UF. Drug use in critically ill patients with acute renal failure. In: Bellomo R, Romeo C, editors. Acute renal failure in the critically ill. Berlin: Springer-Verlag, 1996: 407–34.
Moller JC, Gilman JT, Kearns GL, et al. Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep. Crit Care Med 1992; 20: 1454–8.
Dagan O, Klein J, Gruenwald C, et al. Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Ther Drug Monit 1993; 15: 263–6.
Shelly MP, Cory EP, Park GR. Pharmacokinetics of morphine in two children before and after liver transplantation. Br J Anaesth 1986; 58: 1218–23.
Osborne RJ, Joel SP, Slevin ML. Morphine intoxication in renal failure: the role of morphine-6-glucuronide. BMJ Clin Res Ed 1994; 1986: 1548–9.
Bauer TM, Ritz R, Haberthur C, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995; 346: 145–7.
Touchette MA, Patel RV, Anandan JV, et al. Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically ill patients with end-stage renal disease. Am J Kidney Dis 1995; 26: 469–74.
Kihara M, Ikeda Y, Shibata K, et al. Pharmacokinetic profiles of intravenous imipenem/cilastatin during slow hemodialysis in critically ill patients. Clin Nephrol 1994; 42: 193–7.
Fish DN, Bainbridge JL, Peloquin CA. Variable disposition of ciprofloxacin in critically ill patients undergoing continuous arteriovenous hemodiafiltration. Pharmacotherapy 1995; 15: 236–45.
Kihara M, Ikeda Y, Takagi N, et al. Pharmacokinetics of singledose intravenous amikacin in critically ill patients undergoing slow hemodialysis. Intens Care Med 1995; 21: 348–51.
Davies SP, Lacey LF, Kox WJ, et al. Pharmacokinetics of cefuroxime and ceftazidime in patients with acute renal failure treated by continuous arteriovenous haemodialysis. Nephrol Dialysis Transplant 1991; 6: 971–6.
Reetze-Bonorden P, Bohler J, Keller E. Drug dosage in patients during continuous renal replacement therapy: pharmacokinetic and therapeutic considerations. Clin Pharmacokinet 1993; 24: 362–79.
Ernest D, Cutler DJ. Gentamicin clearance during continuous arteriovenous hemodiafiltration. Crit Care Med 1992; 20: 586–9.
Armstrong DK, Hodgman T, Visconti JA, et al. Hemodialysis of amikacin in critically ill patients. Crit Care Med 1988; 16: 517–20.
Schetz M, Ferdinande P, Van den Berghe G, et al. Pharmacokinetics of continuous renal replacement therapy. Intens Care Med 1995; 21: 612–20.
Keller E, Fecht H, Bohler J, et al. Single-dose kinetics of imipenem/cilastatin during continuous arteriovenous haemofiltration in intensive care patients. Nephrol Dialysis Transplant 1989; 4: 640–5.
Przechera M, Bengel D, Risler T. Pharmacokinetics of imipenem/cilastatin during continuous arteriovenous hemofiltration. Contrib Nephrol 1991; 93: 131–4.
Reetze-Bonorden P, Bohler J, Kohler C, et al. Elimination of vancomycin in patients on continuous arteriovenous hemodialysis. Contrib Nephrol 1991; 93: 135–9.
Randall CTC, Tett SE. Phenytoin pharmacokinetics after intravenous administration to patients receiving enterai tube feeding. Pharm World Sci 1994; 16: 217–24.
Robert S, Zarowitz BJ, Peterson EL, et al. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med 1993; 21: 1487–95.
Reves JG, Fragen RJ, Vinik HR, et al. Midazolam: pharmacology and uses. Anesthesiology 1985; 62: 310–24.
Aitkenhead AR, Pepperman ML, Willatts SM, et al. Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 1989; II: 704–9.
Shapiro JM, Westphal LM, White PF, et al. Midazolam infusion for sedation in the intensive care unit: effect on adrenal function. Anesthesiology 1986; 64: 394–8.
Smith MT, Eadie MJ, Brophy TO. The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol 1981; 19: 271–8.
Harper KW, Collier PS, Dundee JW, et al. Age and nature of operation influence the pharmacokinetics of midazolam. Br J Anaesth 1985; 57: 866–71.
Amrein R, Hetzel W. Pharmacology of Dormicum (midazolam) and Anexate (flumazenil). Acta Anaesth Scand 1994; 92 Suppl.: 6–15.
Allonen H, Ziegler G, Klotz U. Midazolam kinetics. Clin Pharmacol Ther 1981; 30: 653–61.
Mandema JW, Tuk B, van Steveninck AL, et al. Pharmacokinetic-phannacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers. Clin Pharmacol Ther 1992; 51: 715–28.
Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 1984; 61: 27–35.
Ziegler WH, Schalch E, Leishman B, et al. Comparison of the effects of intravenously administered midazolam, triazolam and their hydroxy metabolites. Br J Clin Pharmacol 1983; 16 Suppl. 1: 63S–9S.
Lauven PM, Schwilden H, Stoeckel H, et al. The effects of a benzodiazepine antagonist Ro 15-1788 in the presence of stable concentrations of midazolam. Anesthesiology 1985; 63: 61–4.
Kanto J, Aaltonen L, Himberg JJ, et al. Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study. Anesth Analg 1986; 65: 15–20.
Halliday NJ, Dundee JW, Collier PS, et al. Influence of plasma proteins on the onset of hypnotic action of intravenous midazolam. Anaesthesia 1985; 40: 763–6.
Vinik HR, Reves JG, Greenblatt DJ, et al. The pharmacokinetics of midazolam in chronic renal failure patients. Anesthesiology 1983; 59: 390–4.
Trouvin JH, Farinotti R, Haberer JP, et al. Pharmacokinetics of midazolam in anaesthetized cirrhotic patients. Br J Anaesth 1988; 60: 762–7.
Rinetti M, Ascalone V, Colombi Zinelli L, et al. A pharmacokinetic study on midazolam in compensated liver cirrhosis. Int J Clin Pharmacol Res 1985; 5: 405–11.
MacGilchrist AJ, Birnie GG, Cook A, et al. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut 1986; 27: 190–5.
Shafer A, Doze VA, White PR. Pharmacokinetic variability of midazolam infusions in critically ill patients. Crit Care Med 1990; 18: 1039–41.
Oldenhof H, de Jong M, Steenhoek A, et al. Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability? Clin Pharmacol Ther 1988; 43: 263–9.
Michalk S, Moncorge C, Fichelle A, et al. Midazolam infusion for basal sedation in intensive care: absence of accumulation. Intens Care Med 1988; 15: 37–41.
Byatt CM, Lewis LD, Dawling S, et al. Accumulation of midazolam after repeated dosage in patients receiving mechanical ventilation in an intensive care unit. BMJ Clin Res Ed 1994; 1984: 799–800.
Byrne A, Yeoman PM, Mace P. Accumulation of midazolam in patients receiving mechanical ventilation [letter]. BMJ 1984; 289: 1309.
Malacrida R, Fritz ME, Suter PM, et al. Pharmacokinetics of midazolam administered by continuous intravenous infusion to intensive care patients. Crit Care Med 1992; 20: 1123–6.
Vree TB, Shimoda M, Driessen JJ, et al. Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. Clin Pharmacol Ther 1989; 46: 537–44.
Dirksen MS, Vree TB, Driessen JJ. Clinical pharmacokinetics of long-term infusion of midazolam in critically ill patientspreliminary results. Anaesth Intens Care 1987; 15: 440–4.
Driessen JJ, Vree TB, Guelen PJ. The effects of acute changes in renal function on the pharmacokinetics of midazolam during long-term infusion in ICU patients. Acta Anaesthesiol Belg 1991; 42: 149–55.
Maitre PO, Funk B, Crevoisier C, et al. Pharmacokinetics of midazolam in patients recovering from cardiac surgery. Eur J Clin Pharmacol 1989; 37: 161–6.
Gamble JA, Dundee JW, Gray RC. Plasma diazepam concentrations following prolonged administration. Br J Anaesth 1976; 48: 1087–90.
Herman RJ, Wilkinson GR. Disposition of diazepam in young and elderly subjects after acute and chronic dosing. Br J Clin Pharmacol 1996; 42: 147–55.
Greenblatt DJ, Laughren TP, Allen MD, et al. Plasma diazepam and desmethyldiazepam concentrations during long-term diazepam therapy. Br J Clin Pharmacol 1981; 11: 35–40.
Klotz U, Antonin KH, Brugel H, et al. Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. Clin Pharmacol Ther 1977; 21: 430–6.
Ochs HR, Greenblatt DJ, Kaschell HJ, et al. Diazepam kinetics in patients with renal insufficiency or hyperthyroidism. Br J Clin Pharmacol 1981; 12: 829–32.
Shapiro BA, Warren J, Egol AB, et al. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary: Society of Critical Care Medicine [see comments]. Crit Care Med 1995; 23: 1596–600.
Bachmann KA, Nunlee M, Martin M, et al. The use of single sample clearance estimates to probe hepatic drug metabolism: handprinting the influence of cigarette smoking on human hepatic drug metabolism. Xenobiotica 1990; 20: 537–47.
Boucher BA, Kuhl DA, Fabian TC, et al. Effect of neurotrauma on hepatic drug clearance. Clin Pharmacol Ther 1991; 50: 87–97.
Shafer A, Doze VA, Shafer SL, et al. Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia. Anesthesiology 1988; 69: 348–56.
Gepts E, Camu F, Cockshott ID, et al. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg 1987; 66: 1256–63.
Veroli P, O’Kelly B, Bertrand F, et al. Extrahepatic metabolism of propofol in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth 1992; 68: 183–6.
Gray PA, Park GR, Cockshott ID, et al. Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation. Xenobiotica 1992; 22: 105–14.
Raoof AA, van Obbergh LJ, de Ville de Goyet J, et al. Extrahepatic glucuronidation of propofol in man: possible contribution of gut wall and kidney. Eur J Clin Pharmacol 1996; 50: 91–6.
McMurray TJ, Collier PS, Carson IW, et al. Propofol sedation after open heart surgery: a clinical and pharmacokinetic study. Anaesthesia 1990; 45: 322–6.
Frenkel C, Schuttler J, Ihmsen H, et al. Pharmacokinetics and pharmacodynamics of propofol/alfentanil infusions for sedation in ICU patients. Intens Care Med 1995; 21: 981–8.
Servin F, Desmonts JM, Haberer JP, et al. Pharmacokinetics and protein binding of propofol in patients with cirrhosis. Anesthesiology 1988; 69: 887–91.
Schuttler J, Ihmsen H. Population pharmacokinetics of propofol [abstract]. Anaesthesiology 1993; 79: A331.
Albanese J, Martin C, Lacarelle B, et al. Pharmacokinetics of long-term propofol infusion used for sedation in ICU patients. Anesthesiology 1990; 73: 214–7.
Bailie GR, Cockshott ID, Douglas EJ, et al. Pharmacokinetics of propofol during and after long-term continuous infusion for maintenance of sedation in ICU patients. Br J Anaesth 1992; 68: 486–91.
Eddleston JM, Pollard BJ, Blades JF, et al. The use of propofol for sedation of critically ill patients undergoing haemodiafiltration. Intens Care Med 1995; 21: 342–7.
Ball M, McQuay HJ, Moore RA, et al. Renal failure and the use of morphine in intensive care. Lancet 1985; I: 784–6.
Milne RW, Nation RL, Somogyi AA, et al. The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Br J Clin Pharmacol 1992; 34: 53–9.
Armstrong PJ, Bersten A. Normeperidine toxicity. Anesth Analg 1986; 65: 536–8.
Szeto HH, Inturrisi CE, Houde R, et al. Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure of cancer. Ann Intern Med 1977; 86: 738–41.
Sanford TJJ, Gutstein HB. Fentanyl, sufentanil and alfentanil: comparative pharmacology. In: Barash PG, Cullen BF, Stoelting RK, editors. Clinical anesthesia. 2nd ed. Philadelphia: JB Lippincott, 1995: 1–20.
Bovill JG, Sebel PS. Pharmacokinetics of high-dose fentanyl: a study in patients undergoing cardiac surgery. Br J Anaesth 1980; 52: 795–801.
Haberer JP, Schoeffler P, Couderc E, et al. Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis. Br J Anaesth 1982; 54: 1267–70.
Alazia M, Levron JC, Guidon MD, et al. Pharmacokinetics of fentanyl (F) during continuous infusion in critically ill patients [abstract]. Anesthesiology 1987; 67: A665.
Katz R, Kelly HW. Pharmacokinetics of continuous infusions of fentanyl in critically ill children. Crit Care Med 1993; 21: 995–1000.
Rosow C. Newer opioid analgesics and antagonists. Anaesth Clin North Am 1988; 6: 319–32.
Chauvin M, Bonnet F, Montembault C, et al. The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient. Anesth Analg 1986; 65: 999–1003.
Chauvin M, Ferrier C, Haberer JP, et al. Sufentanil pharmacokinetics in patients with cirrhosis. Anesth Analg 1989; 68: 1–4.
Yate PM, Thomas D, Short SM, et al. Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU. Br J Anaesth 1986; 58: 1091–9.
Yun CH, Wood M, Wood AJ, et al. Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4: an explanation of the variable elimination clearance. Anesthesiology 1992; 77: 467–74.
Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84: 812–20.
Elliot JM, Bion JF. The use of neuromuscular blocking drugs in intensive care practice. Acta Anaesth Scand 1995; 106 Suppl.: 70–82.
Gooch JL, Suchyta MR, Balbierz JM, et al. Prolonged paralysis after treatment with neuromuscular junction blocking agents [see comments]. Crit Care Med 1991; 19: 1125–31.
Partridge BL, Abrams JH, Bazemore C, et al. Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide in the intensive care unit [see comments]. Crit Care Med 1990; 18: 1177–9.
Leatherman JW, Fluegel WL, David WS, et al. Muscle weakness in mechanically ventilated patients with severe asthma. Am J Respir Crit Care Med 1996; 153: 1686–90.
Khuenl-Brady KS, Reitstatter B, Schlager A, et al. Long-term administration of pancuronium and pipecuronium in the intensive care unit [see comments]. Anesth Analg 1994; 78: 1082–6.
Shapiro BA, Warren J, Egol AB, et al. Practice parameters for sustained neuromuscular blockade in the adult critically ill patient: an executive summary: Society of Critical Care Medicine. Crit Care Med 1995; 23: 1601–5.
Vandenbrom RH, Wierda JM. Pancuronium bromide in the intensive care unit: a case of overdose. Anesthesiology 1988; 69: 996–7.
Ward S, Judge S, Corail I. Pharmacokinetics of pancuronium bromide in liver failure. Br J Anaesth 1982; 54: 227P.
Agoston S, Vandenbrom RH, Wierda JM. Clinical pharmacokinetics of neuromuscular blocking drugs. Clin Pharmacokinet 1992; 22: 94–115.
Agoston S, Vandenbrom RHG, Wierda JMKH. Use of neuromuscular blocking agents in the intensive care unit. In: Partridge BL, editor. Advances in the use of muscle relaxants. Philadelphia: WB Saunders, 1993: 345–59.
Segredo V, Matthay MA, Sharma ML, et al. Prolonged neuromuscular blockade after long-term administration of vecuronium in two critically ill patients. Anesthesiology 1990; 72: 566–70.
Ward S, Weatherley BC. Pharmacokinetics of atracurium and its metabolites. Br J Anaesth 1986; 58 Suppl. 1: 6S–10S.
Parker CJ, Jones JE, Hunter JM. Disposition of infusions of atracurium and its metabolite, laudanosine, in patients in renal and respiratory failure in an ITU. Br J Anaesth 1988; 61: 531–40.
Bion JF, Bowden MI, Chow B, et al. Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation. Intens Care Med 1993; 19 Suppl. 2: S94–8.
Yate PM, Flynn PJ, Arnold RW, et al. Clinical experience and plasma laudanosine concentrations during the infusion of atracurium in the intensive therapy unit. Br J Anaesth 1987; 59: 211–7.
Cook DR, Freeman JA, Lai AA, et al. Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure. Br J Anaesth 1992; 69: 580–5.
deBros F, Goudsouzian N, Chakravorty S, et al. Pharmacokinetic evaluation of the cis-cis isomer, alcohol and ester metabolites of mivacurium during prolonged infusions in neurosurgical patients. Anesthesiology 1994; 81 Suppl. 3A: 1085.
Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993; 37: 1073–81.
Goss TF, Forrest A, Nix DE, et al. Mathematical examination of dual individualization principles. II: the rate of bacterial eradication at the same area under the inhibitory curve is more rapid for ciprofloxacin than for cefmenoxime. Ann Pharmacother 1994; 28: 863–8.
Whipple JK, Ausman RK, Franson T, et al. Effect of individualized pharmacokinetic dosing on patient outcome. Crit Care Med 1991; 19: 1480–5.
Nicolau DP, Crowe H, Nightingale CH, et al. Bioavailability of fluconazole administered via a feeding tube in intensive care unit patients. J Antimicrob Chemother 1995; 36: 395–401.
Chin TW, Vandenbroucke A, Fong IW. Pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients. Antimicrob Agents Chemother 1995; 39: 28–33.
Dive A, Miesse C, Galanti L, et al. Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study. Crit Care Med 1995; 23: 1356–62.
Healy DP, Brodbeck MC, Clendening CE. Ciprofloxacin absorption is impaired in patients given enterai feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother 1996; 40: 6–10.
Barker EM, Aitchison JM, Cridland JS, et al. Rectal administration of metronidazole in severely ill patients. BMJ Clin Res Ed 1994; 1983: 311–3.
Kleinschmidt R, Rommelsheim K, Exner M, et al. The effectiveness of intratracheal antibiotic administration: clinical, microbiologic and pharmacologic results. Anasth Intensivther Notf Med 1989; 24: 143–6.
Bressolle F, de la Coussaye JE, Ayoub R, et al. Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability. Antimicrob Agents Chemother 1992; 36: 1404–11.
Jensen T, Pedersen SS, Garne S, et al. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonus aeruginosa lung infection. J Antimicrob Chemother 1987; 19: 831–8.
Masur H. Prevention and treatment of pneumocystis pneumonia [published erratum appears in N Engl J Med 1993; 328: 1136]. N Engl J Med 1992; 327: 1853–60.
Kropec A, Daschner FD. Penetration into tissues of various drugs active against gram-positive bacteria. J Antimicrob Chemother 1991; 27: Suppl. B: 9–15.
van Dalen R, Vree TB. Pharmacokinetics of antibiotics in critically ill patients. Intens Care Med 1990; 16 Suppl. 3: S235–8.
Sun H, Maderazo EG, Krusell AR. Serum protein-binding characteristics of vancomycin. Antimicrob Agents Chemother 1993; 37: 1132–6.
St Peter WL, Redic-Kill KA, Halstenson CE. Clinical pharmacokinetics of antibiotics in patients with impaired renal function. Clin Pharmacokinet 1992; 22: 169–210.
Elston AC, Bayliss MK, Park GR. Effect of renal failure on drug metabolism by the liver. Br J Anaesth 1993; 71: 282–90.
Slugg PH, Haug MT, Pippenger CE. Ranitidine pharmacokinetics and adverse central nervous system reactions. Arch Intern Med 1992; 152: 2325–9.
Charbonneau P, Harding I, Garaud JJ, et al. Teicoplanin: a welltolerated and easily administered alternative to vancomycin for gram-positive infections in intensive care patients. Intens Care Med 1994; 20 Suppl. 4: S35–42.
Hofmann W, Kroh U, Lennartz H. Infection-induced change in the pharmacokinetics of cefotaxime: dose calculation in multiple organ failure and relevance of score systems. Klin Wochenschr 1991; 69 Suppl. 26: 32–5.
van Dalen R, Vree TB, Baars AM, et al. Dosage adjustment for ceftazidime in patients with impaired renal function. Eur J Clin Pharmacol 1986; 30: 597–605.
Bressolle F, Gouby A, Martinez JM, et al. Population pharmacokinetics of amikacin in critically ill patients. Antimicrob Agents Chemother 1996; 40: 1682–9.
Debord J, Pessis C, Voultoury JC, et al. Population pharmacokinetics of amikacin in intensive care unit patients studied by NPEM algorithm. Fund Clin Pharmacol 1995; 9: 57–61.
Gauthier T, Lacarelle B, Marre F, et al. Predictive performance of two software packages (USC*PACK PC and Abbott PKS system) for the individualization of amikacin dosage in intensive care unit patients. Int J B iomed Comput 1994; 36: 131–4.
Garraffo R, Iliadis A, Cano JP, et al. Application of Bayesian estimation for the prediction of an appropriate dosage regimen of amikacin. J Pharm Sci 1989; 78: 753–7.
Lenert LA, Klostermann H, Coleman RW, et al. Practical computer-assisted dosing for aminoglycoside antibiotics. Antimicrob Agents Chemother 1992; 36: 1230–5.
Kumana CR, Yuen KY. Parenteral aminoglycoside therapy: selection, administration and monitoring [review]. Drugs 1994; 47: 902–13.
Hickling K, Begg E, Moore ML. A prospective randomised trial comparing individualised pharmacokinetic dosage prediction for aminoglycosides with prediction based on estimated creatinine clearance in critically ill patients. Intens Care Med 1989; 15: 233–7.
Pryka RD, Rodvold KA, Erdman SM. An updated comparison of drug dosing methods. IV: vancomycin. Clin Pharmacokinet 1991; 20: 463–76.
Reed RL, Wu AH, Miller-Crotchett P, et al. Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients. J Trauma 1989; 29: 1462–8.
Zarowitz BJ, Robert S, Mlynarek M, et al. Determination of gentamicin pharmacokinetics by bioelectrical impedance in critically ill adults. J Clin Pharmacol 1993; 33: 562–7.
Jelliffe RW, Iglesias T, Hurst AK, et al. Individualising gentamicin dosage regimens: a comparative review of selected models, data fitting methods and monitoring strategies [review]. Clin Pharmacokinet 1991; 21: 461–78.
Notterman DA, Greenwald BM, Moran F, et al. Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction. Clin Pharmacol Ther 1990; 48: 138–47.
Marik PE. Aminoglycoside volume of distribution and illness severity in critically ill septic patients. Anaesth Intens Care 1993; 21: 172–3.
Lacarelle B, Granthil C, Manelli JC, et al. Evaluation of a Bayesian method of amikacin dosing in intensive care unit patients with normal or impaired renal function. Ther Drug Monit 1987; 9: 154–60.
Armendariz E, Chelluri L, Ptachcinski R. Pharmacokinetics of amikacin during continuous veno-venous hemofiltration. Crit Care Med 1990; 18: 675–6.
Triginer C, Izquierdo I, Fernandez R, et al. Gentamicin volume of distribution in critically ill septic patients. Intens Care Med 1990; 16: 303–6.
Dasta JF, Armstrong DK. Variability in aminoglycoside pharmacokinetics in critically ill surgical patients. Crit Care Med 1988; 16: 327–30.
Benet LZ, Zech K. Pharmacokinetics: a relevant factor for the choice of a drug? Aliment Pharmacol Ther 1994; 8 Suppl. 1: 25–32.
Martin C, Thomachot L, Albanese J. Clinical pharmacokinetics of cefotetan. Clin Pharmacokinet 1994; 26: 248–58.
Rondanelli R, Dionigi RV, Regazzi MB, et al. Ceftazidime in the treatment of Pseudomonas infections in intensive-care patients. Int J Clin Pharmacol Ther Toxicol 1986; 24: 457–9.
Strenkoski LC, Nix DE. Cefpirome clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 263–73.
Heinemeyer G, Link J, Weber W, et al. Clearance of ceftriaxone in critical care patients with acute renal failure. Intens Care Med 1990; 16: 448–53.
Mattie H. Clinical pharmacokinetics of aztreonam: an update. Clin Pharmacokinet 1994; 26: 99–106.
Vos MC, Vincent HH, Yzerman EP. Clearance of imipenem/cilastatin in acute renal failure patients treated by continuous hemodiafiltration (CAVHD). Intens Care Med 1992; 18: 282–5.
Ambrose PJ. Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate. Clin Pharmacokinet 1984; 9: 222–38.
Murphy S, Pinney RJ. Teicoplanin or vancomycin in the treatment of gram-positive infections? J Clin Pharm Ther 1995; 20: 5–11.
Hillaire-Buys D, Peyriere H, Lobjoie E, et al. Influence of arterio-venous haemofiltration on teicoplanin elimination. Br J Clin Pharmacol 1995; 40: 95–7.
Wolter K, Claus M, Wagner K, et al. Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis. Clin Nephrol 1994; 42: 389–97.
Brogden RN, Peters DH. Teicoplanin: a reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47: 823–54.
Santre C, Leroy O, Simon M, et al. Pharmacokinetics of vancomycin during continuous hemodiafiltration. Intens Care Med 1993; 19: 347–50.
Mazzei T, Surrenti C, Novelli A, et al. Pharmacokinetics of azithromycin in patients with impaired hepatic function. J Antimicrob Chemother 1993; 31 Suppl. E: 57–63.
Dunn CJ, Barradell LB. Azithromycin: a review of its pharmacological properties and use as a 3-day therapy in respiratory tract infections. Drugs 1996; 51: 483–505.
Plaisance KI, Drusano GL, Forrest A, et al. Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate. Antimicrob Agents Chemother 1989; 33: 618–20.
Sorgel F, Kinzig M. Pharmacokinetic characteristics of piperacillin/tazobactam. Intens Care Med 1994; 20 Suppl. 3: S14–20.
Johnson CA, Halstenson CE, Kelloway JS, et al. Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. Clin Pharmacol Ther 1992; 51: 32–41.
Forrest A, Ballow CH, Nix DE, et al. Development of a population pharmacokinetic model and optimal sampling strategies for intravenous ciprofloxacin. Antimicrob Agents Chemother 1993; 37: 1065–72.
Lipman J, Scribante J, Pinder M, et al. Serum levels of ciprofloxacin (400 mg IVI Q8H) in severe sepsis. Intens Care Med 1996; 22: S392.
Hess MM, Boucher BA, Laizure SC, et al. Trimethoprimsulfamethoxazole pharmacokinetics in trauma patients. Pharmacotherapy 1993; 13: 602–6.
Raghuram TC, Krishnaswamy K. Pharmacokinetics of tetracycline in nutritional edema. Chemotherapy 1982; 28: 428–33.
Houghton GW, Dennis MJ, Gabriel R. Pharmacokinetics of metronidazole in patients with varying degrees of renal failure. Br J Clin Pharmacol 1985; 19: 203–9.
Ljungberg B, Nilsson-Ehle I, Ursing B. Metronidazole: pharmacokinetic observations in severely ill patients. J Antimicrob Chemother 1984; 14: 275–83.
Lau AH, Lam NP, Piscitelli SC, et al. Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives. Clin Pharmacokinet 1992; 23: 328–64.
Israili ZH, Rogers CM, el-Attar H. Pharmacokinetics of antituberculosis drugs in patients. J Clin Pharmacol 1987; 27: 78–83.
Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Revs Infect Dis 1990; 12: 308–29.
Kowalsky SF, Dixon DM. Fluconazole: a new antifungal agent [review]. Clin Pharm 1991; 10: 179–94.
Nicolau DP, Crowe H, Nightingale CH, et al. Effect of continuous arteriovenous hemodiafiltration on the pharmacokinetics of fluconazole. Pharmacotherapy 1994; 14: 502–5.
Fabris A, Pellanda MV, Gardin C, et al. Pharmacokinetics of antifungal agents. Peritoneal Dialysis International 1993; 13 Suppl. 2: S380–2.
Boelaert J, Schurgers M, Matthys E, et al. Itraconazole pharmacokinetics in patients with renal dysfunction. Antimicrob Agents Chemother 1988; 32: 1595–7.
Cauwenbergh G. Pharmacokinetics of itraconazole [review, in German]. Mycoses 1994; 37 Suppl. 2: 27–33.
Lampe D, Kreutzberg S, Prumke HJ. Therapeutic drug monitoring of itraconazole: a report of experiences [in German]. Mycoses 1994; 37 Suppl. 2: 34–9.
Almond MK, Fan S, Dhillon S, et al. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron 1995; 69: 428–32.
O’Brien JJ, Campoli-Richards DM. Acyclovir: an updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989; 37: 233–309.
Laskin OL. Clinical pharmacokinetics of acyclovir. Clin Pharmacokinet 1983; 8: 187–201.
Morse GD, Shelton MJ, O’Donnell AM. Comparative pharmacokinetics of antiviral nucleoside analogues. Clin Pharmacokinet 1993; 24: 101–23.
Aweeka FT, Gambertoglio JG, Kramer F, et al. Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis. Clin Pharmacol Ther 1995; 57: 403–12.
Markham A, Faulds D. Ganciclovir: an update of its therapeutic use in cytomegalovirus infection. Drugs 1994; 48: 455–84.
Benet LZ, Oie S, Schwartz JB. Appendix II: design and optimisation of dosage regimens; pharmacokinetic data. In: Hardman JG, Limbird LE, Molinoff PB, editor. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 1707–92.
Badewitz-Dodd LH, editor. MIMS Australia. Sydney: Medi Media, 1996.
Reynolds JEF, editor. Martindale: the extra pharmacopoeia. London: The Pharmaceutical Press, 1996.
Mazzei T, Novelli A, De Lalla F, et al. Tissue penetration and pulmonary disposition of tobramycin. J Chemother 1995; 7: 363–70.
Santre C, Georges H, Jacquier JM, et al. Amikacin levels in bronchial secretions of 10 pneumonia patients with respiratory support treated once daily versus twice daily. Antimicrob Agents Chemother 1995; 39: 264–7.
Barclay ML, Begg EJ, Hickling KG. What is the evidence for once-daily aminoglycoside therapy? Clin Pharmacokinet 1994; 27: 32–48.
Nicolau DP, Freeman CD, Belliveau PP, et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother 1995; 39: 650–5.
Novelli A, Mazzei T, Fallani S, et al. In vitro postantibiotic effect and postantibiotic leukocyte enhancement of tobramycin. J Chemother 1995; 7: 355–62.
Barza M, Ioannidis JP, Cappelleri JC, et al. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ 1996; 312: 338–45.
Marra F, Bonewald LF, Park-Snyder S, et al. Characterization and regulation of the latent transforming growth factor-beta complex secreted by vascular pericytes. J Cell Physiol 1996; 166: 537–46.
Hickling KG, Begg EJ, Perry RE, et al. Serum aminoglycoside clearance is predicted as poorly by renal aminoglycoside clearance as by creatinine clearance in critically ill patients. Crit Care Med 1991; 19: 1041–7.
Watling SM, Kisor DF. Population pharmacokinetics: development of a medical intensive care unit-specific gentamicin dosing nomogram. Ann Pharmacother 1993; 27: 151–4.
Debord J, Voultoury JC, Lachatre G, et al. Pharmacokinetics and dosage regimens of amikacin in intensive care unit patients. Int J Biomed Comput 1994; 36: 135–7.
Buylaert WA, Herregods LL, Mortier EP, et al. Cardiopulmonary bypass and the pharmacokinetics of drugs: an update. Clin Pharmacokinet 1989; 17: 10–26.
Miglioli PA, Merlo F, Campanile F, et al. Effects of cardiopulmonary bypass on teicoplanin serum disposition. Int J Clin Pharmacol Res 1995; 15: 23–5.
Pryka RD, Rodvold KA, Ting W, et al. Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin disposition. Antimicrob Agents Chemother 1993; 37: 2106–11.
Nau R, Prange HW, Muth P, et al. Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. Antimicrob Agents Chemother 1993; 37: 1518–24.
Young RJ, Lipman J, Gin T, et al. Do the recommended ceftazidime regimens maintain optimal plasma concentrations in critically ill patients?. Intens Care Med 1996; 22 Suppl. 3: S392.
Mouton JW, den Hollander JG. Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model. Antimicrob Agents Chemother 1994; 38: 931–6.
Stoeckel K, Koup JR. Pharmacokinetics of ceftriaxone in patients with renal and liver insufficiency and correlations with a physiologic nonlinear protein binding model. Am J Med 1984; 77: 26–32.
Yuk-Choi JH, Nightingale CH, Williams Jr TW. Considerations in dosage selection for third generation cephalosporins. Clin Pharmacokinet 1992; 22: 132–43.
Losno Garcia R, Santivanez V, Battilana CA. Single-dose pharmacokinetics of ceftriaxone in patients with end-stage renal disease and hemodialysis [published erratum appears in Chemotherapy 1989; 35 (3): 235]. Chemotherapy 1988; 34: 261–6.
Keller E, Bohler J, Busse-Grawitz A, et al. Single dose kinetics of piperacillin during continuous arteriovenous hemodialysis in intensive care patients. Clin Nephrol 1995; 43 Suppl. 1: S20–3.
Fabre D, Bressolle F, Gomeni R, et al. Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa. Antimicrob Agents Chemother 1991; 35: 2521–5.
Schwartz J, Jauregui L, Lettieri J, et al. Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum. Antimicrob Agents Chemother 1988; 32: 75–7.
Yuen GJ, Drusano GL, Forrest A, et al. Prospective use of optimal sampling theory: steady-state ciprofloxacin pharmacokinetics in critically ill trauma patients. Clin Pharmacol Ther 1989; 46: 451–7.
Buijk SLCE, Van den Berg MFQ, Mouton JW, et al. Bioavailability of ciprofloxacin after multiple oral and intravenous doses in intensive care patients with gram negative intra-abdominal infections. Intens Care Med 1996; 22 Suppl. 3: S391.
Yuk JH, Nightingale CH, Sweeney KR, et al. Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enterai feeding. Antimicrob Agents Chemother 1989; 33: 1118–20.
Mueller BA, Brierton DG, Abel SR, et al. Effect of enterai feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother 1994; 38: 2101–5.
Frost RW, Lasseter KC, Noe AJ, et al. Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin. Antimicrob Agents Chemother 1992; 36: 830–2.
Bressolle F, Goncalves F, Gouby A, et al. Pefloxacin clinical pharmacokinetics. Clin Pharmacokinet 1994; 27: 418–46.
Lamp KC, Bailey EM, Rybak MJ. Ofloxacin clinical pharmacokinetics [review]. Clin Pharmacokinet 1992; 22: 32–46.
Alarabi AA, Cars O, Danielson BG, et al. Pharmacokinetics of intravenous imipenem/cilastatin during intermittent haemofiltration. J Antimicrob Chemother 1990; 26: 91–8.
Clissold SP, Todd PA, Campoli-Richards DM. Imipenem/cilastatin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1987; 33: 183–241.
Drusano GL, Hutchison M. The pharmacokinetics of meropenem. Scand J Infect Dis 1995; Suppl. 96: 11–6.
Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet 1995; 28: 275–86.
Ackerman BH, Vannier AM. Necessity of a loading dose when using vancomycin in critically ill patients. J Antimicrob Chemother 1992; 29: 460–1.
Lamer C, de Beco V, Soler P, et al. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob Agents Chemother 1993; 37: 281–6.
Luer MS, Hatton J. Vancomycin administration into the cerebrospinal fluid: a review. Ann Pharmacother 1993; 27: 912–21.
Leader WG, Chandler MH, Castiglia M. Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet 1995; 28: 327–42.
Trautmann M, Wiedeck H, Ruhnke M, et al. Teicoplanin: 10 years of clinical experience. Infection 1994; 22: 430–6.
Mann HJ, Townsend RJ, Fuhs DW, et al. Decreased hepatic clearance of clindamycin in critically ill patients with sepsis. Clin Pharm 1987; 6: 154–9.
Periti P, Mazzei T, Mini E, et al. Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet 1992; 23: 106–31.
Singlas E. Clinical pharmacokinetics of azithromycin. Pathol Biol 1995; 43: 505–11.
Chopra I, Hawkey PM, Hinton M. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother 1992; 29: 245–77.
Neuvonen PJ, Penttila O. Interaction between doxycycline and barbiturates. BMJ 1974; I: 535–6.
Penttila O, Neuvonen PJ, Aho K, et al. Interaction between doxycycline and some antiepileptic drugs. BMJ 1974; 2: 470–2.
Plaisance KI, Quintiliani R, Nightingale CH. The pharmacokinetics of metronidazole and its metabolites in critically ill patients. J Antimicrob Chemother 1988; 21: 195–200.
Kerremans AL. Cytochrome P450 isoenzymes: importance for the internist. Neth J Med 1996; 48: 237–43.
Chandler MH, Toler SM, Rapp RP, et al. Multiple-dose pharmacokinetics of concurrent oral ciprofloxacin and rifampin therapy in elderly patients. Antimicrob Agents Chemother 1990; 34: 442–7.
Debruyne D, Ryckelynck JP. Clinical pharmacokinetics of fluconazole. Clin Pharmacokinet 1993; 24: 10–27.
Thaler F, Bernard B, Tod M, et al. Fluconazole penetration in cerebral parenchyma in humans at steady state. Antimicrob Agents Chemother 1995; 39: 1154–6.
Janknegt R, de Marie S, Bakker-Woudenberg IA, et al. Liposomal and lipid formulations of amphotericin B: clinical pharmacokinetics. Clin Pharmacokinet 1992; 23: 279–91.
Hoffman BB, Lefkowitz RJ. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, Molinoff PB, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. New York: McGraw-Hill, 1996: 199–248.
Kulka PJ, Tryba M. Inotropic support of the critically ill patient: a review of the agents. Drugs 1993; 45: 654–67.
Lisbom A, Van der Salm TJ, Visner MS. Management of the postoperative cardiac surgical patient. In: Rippe JM, Irwin RS, Fink MP, editors. Intensive care medicine. Boston: Little Brown & Company, 1996: 1764–81.
Sumikawa K, Hayashi Y, Yamatodani A, et al. Contribution of the lungs to the clearance of exogenous dopamine in humans. Anesth Analg 1991; 72: 622–6.
Ratge D, Gehrke A, Melzner I, et al. Free and conjugated catecholamines in human plasma during physical exercise. Clin Exp Pharmacol Physiol 1986; 13: 543–53.
Le Corre P, Malledant Y, Tanguy M, et al. Steady-state pharmacokinetics of dopamine in adult patients. Crit Care Med 1993; 21: 1652–7.
Eldadah MK, Schwartz PH, Harrison R, et al. Pharmacokinetics of dopamine in infants and children. Crit Care Med 1991; 19: 1008–11.
Bhatt-Mehta V, Nahata MC, McClead RE, et al. Dopamine pharmacokinetics in critically ill newborn infants. Eur J Clin Pharmacol 1991; 40: 593–7.
Bhatt-Mehta V, Nahata MC. Dopamine and dobutamine in pediatric therapy. Pharmacotherapy 1989; 9: 303–14.
Zaritsky A, Lotze A, Stull R, et al. Steady-state dopamine clearance in critically ill infants and children. Crit Care Med 1988; 16: 217–20.
Padbury JF, Agata Y, Baylen BG, et al. Pharmacokinetics of dopamine in critically ill newborn infants. J Paediatr 1990; 117: 472–6.
Klem C, Dasta JF, Reilley TE, et al. Variability in dobutamine pharmacokinetics in unstable critically ill surgical patients. Crit Care Med 1994; 22: 1926–32.
Kates RE, Leier CV. Dobutamine pharmacokinetics in severe heart failure. Clin Pharmacol Ther 1978; 24: 537–41.
Klem C, Dasta JF, Reilley TE, et al. Pulmonary extraction of dobutamine in critically ill surgical patients. Anesth Analg 1995; 81: 287–91.
Maynard ND, Bihari DJ, Dalton RN, et al. Increasing splanchnic blood flow in the critically ill. Chest 1995; 108: 1648–54.
Gray PA, Jones T, Park GR. Blood concentrations of dopexamine in patients during and after orthotopic liver transplantation. Br J Clin Pharmacol 1994; 37: 89–92.
Neale MG, Baker P, Brown K, et al. Pharmacokinetics and metabolism of dopexamine in man. Acta Pharmacol Toxicol 1986; 59 Suppl. V: 69.
Stroshane RM, Koss RF, Biddlecome CE, et al. Oral and intravenous pharmacokinetics of milrinone in human volunteers. J Pharm Sci 1984; 73: 1438–41.
Hamilton RA, Kowalsky SF, Wright EM, et al. Effect of the acetylator phenotype on amrinone pharmacokinetics. Clin Pharmacol Ther 1986; 40: 615–9.
Steinberg C, Notterman DA. Pharmacokinetics of cardiovascular drugs in children: inotropes and vasopressors. Clin Pharmacokinet 1994; 27: 345–67.
Baim DS. Effect of phosphodiesterase inhibition on myocardial oxygen consumption and coronary blood flow. Am J Cardiol 1989; 63: 23A–6A.
Ross MP, Allen-Webb EM, Pappas JB, et al. Amrinone-associated thrombocytopenia: pharmacokinetic analysis. Clin Pharmacol Ther 1993; 53: 661–7.
Butterworth JF, Hines RL, Royster RL, et al. A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery. Anesth Analg 1995; 81: 783–92.
Bailey JM, Levy JH, Kikura M, et al. Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery. Anesthesiology 1994; 81: 616–22.
Prielipp RC, MacGregor DA, Butterworth JF, et al. Pharmacodynamics and pharmacokinetics of milrinone administration to increase oxygen delivery in critically ill patients. Chest 1996; 109: 1291–301.
Ostro MJ. Pharmacodynamics and pharmacokinetics of parenteral histamine (H2)-receptor antagonists. Am J Med 1987; 83: 15–22.
Gladziwa U, Klotz U. Pharmacokinetics and pharmacodynamics of H2 receptor antagonists in patients with renal insufficiency. Clin Pharmacokinet 1993; 24: 319–32.
Nation RL, Ilett KF, Tjokrosetio R, et al. Pharmacokinetics of cimetidine in critically ill patients. Eur J Clin Pharmacol 1984; 26: 341–6.
Pancorbo S, Bubrick MP, Chin TW, et al. Cimetidine dynamics after single intravenous doses. Clin Pharmacol Ther 1982; 31: 83–8.
Ilett KF, Nation RL, Tjokrosetio R, et al. Pharmacokinetics of ranitidine in critically ill patients. Br J Clin Pharmacol 1986; 21: 279–88.
Geus WP, Vinks AATMM, Lamers CBHW. Pharmacokinetics of ranitidine in a homogeneous population of intensive care unit patients during intermittent and continuous administration. Scand J Gastroenterol 1992; 27 Suppl. 194: 55–8.
Yate PM, Arnold RW, Flynn PJ, et al. Atracurium infusions in the intensive care unit including measurement of laudanosine [abstract]. Anesthesiology 1992; 63: A313.
Andersson T, Olsson R, Regardh CG, et al. Pharmacokinetics of [14C]omeprazole in patients with liver cirrhosis. Clin Pharmacokinet 1993; 24: 71–8.
Andersson T, Andren K, Cederberg C, et al. Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects. Br J Clin Pharmacol 1990; 29: 557–63.
Cederberg C, Andersson T, Skanberg I. Omeprazole: phannacokinetics and metabolism in man. Scand J Gastroenterol 1989; 166 Suppl.: 33–40.
Delhotal-Landes B, Flouvat B, Duchier J, et al. Pharmacokinetics of lansoprazole in patients with renal or liver disease of varying severity. Eur J Clin Pharmacol 1993; 45: 367–71.
Wilde MI, McTavish D. Omeprazole: an update of its phannacology and therapeutic use in acid-related disorders. Drugs 1994; 48: 91–132.
Pue MA, Laroche J, Meineke I, et al. Pharmacokinetics of pantoprazole following single intraveous and oral administration to healthy male subjects. Eur J Clin Pharmacol 1993; 44: 575–8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Power, B.M., Forbes, A.M., van Heerden, P.V. et al. Pharmacokinetics of Drugs Used in Critically Ill Adults. Clin Pharmacokinet 34, 25–56 (1998). https://doi.org/10.2165/00003088-199834010-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199834010-00002