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Wheeless' Textbook of Orthopaedics

Kinetic model for gentamicin dosing with the use of individual patient


parameters. Sawchuk RJ. Zaske DE. Cipolle RJ. Wargin WA. Strate RG. Clinical Pharmacology & Therapeutics. [JC:dhr] 21(3):362-9, 1977 Mar. Multiple-infusion dosing regimens for gentamicin were established for 84 patients with the use of individually calculated values of elimination kinetic parameters. Serum level-time data obtained after a single infusion were used to determine the patient's gentamicin half-life (t 1/2) and distribution volume. Patients with serum creatinine (Cr) less than 1.2 mg per 100 ml had t 1/2 (mean, 2.25 hr) and total body clearances (mean, 0.082 L/hr/kg) significantly different from those with Cr greater than or equal to 1.2 mg/100 ml (means, 5.3 and 0.039, respectively). Distribution volumes were not significantly different (means, 0.22 and 0.21 L/kg, respectively). Calculations of dosing intervals and infusion rates, based on each patient's kinetic parameters and desired steady-state peaks and nadirs, assumed a one-compartment model with first-order elimination and 1 -hr constant-rate input at fixed intervals. Follow-up steady-state peak and nadir levels were measured in 63 of the regimens. Differences between predicted and measured peak levels averaged --0.05 mug/ml with 60% of the measured values falling within 1 mug/ml of that predicted. Predicted -measured nadir differences averaged --0.62 mug/ml (significantly different from zero) indicating slight bias in the model. Fifty-six percent of these nadirs were within 1 mug/ml of that predicted.



Original Text by Clifford R. Wheeless, III, MD.