Kinetic model for gentamicin dosing with the use of individual patient parameters

Abstract

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) <1.2 mg per 100 ml had t 1 2 (mean, 2.25 hr) and total body clearances (mean, 0.082 Llhrlkg) significantly different from those with Cr ≥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 μg/ml with 60% of the measured values falling within μg/ml of that predicted. Predicted-measured nadir differences averaged -0.62 μg/ml (significantly different from zero) indicating slight bias in the model. Fifty-six percent of these nadirs were within l μg/ml of that predicted. © 1977.