Intensive Care Medicine

, Volume 15, Issue 4, pp 233–237 | Cite as

A prospective randomised trial comparing individualised pharmacokinetic dosage prediction for aminoglycosides with prediction based on estimated creatinine clearance in critically ill patients

  • K. Hickling
  • E. Begg
  • M. L. Moore
Original Articles

Abstract

A prospective randomised trial was conducted in critically ill patients to evaluate a computer aided pharmacokinetic method of aminoglycoside dose prediction based on 3 measured plasma concentrations following the loading dose. The ability of this method to achieve therapeutic plasma aminoglycoside concentrations early in the course of treatment was compared with that of a nomogram approach based on creatinine clearance estimated using the formula of Cock-roft and Gault. Ninety-two percent of patients in the computer group achieved peak plasma concentrations within the optimum range of 6–10 mg/l at 48–72 h compared with 21% of control group patients (p=0.0009). The mean peak plasma concentration of 7.45 mg/l at 48–72 h in the computer group was closer to the target concentration of 8 mg/l than was the 5.14 mg/l in the control group (p=0.0004). There was no significant difference between the groups in measured indices of renal function, both groups showing an improvement in mean estimated creatinine clearance from the beginning to the end of the course of treatment. Dosing based on individualised pharmacokinetic data is therefore a more reliable method of achieving therapeutic blood concentrations early in the course of treatment than is nomogram based dosing. Other studies suggest that this should be associated with a reduction in mortality in severe infections.

Key words

Aminoglycosides Pharmacokenetic dosing 

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References

  1. 1.
    Cockroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31Google Scholar
  2. 2.
    Davey PG, Geddes AM, Gonda I (1984) Comparison of methods for estimating gentamicin clearance and retrospective analysis of changes in clearnance with emphasis on patients with normal renal function. Br J Clin Pharmacol 17:147–155Google Scholar
  3. 3.
    Evans WE, Taylor RH, Feldman S (1980) A model for dosing gentamicin in children and adolescents that adjusts for tissue accumulation with continuous dosing. Clin Pharmacokinet 5:295–306Google Scholar
  4. 4.
    Sande MA, Mandell HG (1985) Aminoglycosides. In: Goodman, Gilman A et al (eds) The pharmacological basis of therapeutics, 7th edn. MacMillan, New York, p 1154Google Scholar
  5. 5.
    Moore RD, Smith CR, Lietman PS (1984) The association of aminoglycoside plasma levels with mortality in patients with gram negative bacteremia. J Infect Dis 149:443–448Google Scholar
  6. 6.
    Moore RD, Smith CR, Lietman PS (1984) Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med 77:657–662Google Scholar
  7. 7.
    Moore RD, Lietman PS, Smith CR (1987) Clinical response to aminoglycoside therapy: Importance of ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155:93–99Google Scholar
  8. 8.
    Oates JA, Wilkinson GR (1987) Clinical pharmacology. In: Braunwald E et al. (eds) Harrison's principles of internal medicine. McGraw Hill, New York, 11th edn, p 347Google Scholar
  9. 9.
    Sawchuk RJ, Zaske DE, Cipolle RJ (1977) Kinetic model for gentamicin dosing with the use of individual patient parameters. Clin Pharmacol Ther 21:362–365Google Scholar
  10. 10.
    Summer WR, Michael JR, Lipsky JJ (1983) Initial aminoglycoside levels in the critically ill. Crit Care Med 11:948–950Google Scholar
  11. 11.
    Zaske DE, Cipolle RJ, Strate RJ (1980) Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function. Surgery 87:164–169Google Scholar
  12. 12.
    Zaske DE, Bootman JL, Solem LB (1982) Increased burn patient survival with individualised doses of gentamicin. Surgery 91:142–149Google Scholar
  13. 13.
    Zaske DE, Cipolle RJ, Rotschafer JC (1982) Gentamicin kinetics in 1640 patients: Method for control of serum concentrations. Antimicrob Agents Chemother 21:407–411Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • K. Hickling
    • 1
  • E. Begg
    • 2
  • M. L. Moore
    • 1
  1. 1.Department of Intensive CareChristchurch HospitalChristchurchNew Zealand
  2. 2.Department of Clinical PharmacologyChristchurch HospitalChristchurchNew Zealand

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