Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients

A general approach to the establishment of dosing regimens for drug administration by multiple intravenous infusions is presented. The method is applicable where the elimination kinetics are first order and can be represented by a one-compartment open model. The approach utilizes serum concentration-time data obtained during any dosing interval for the calculation of the apparent distribution volume and the half-life in individual patients. These values are then used to individualize the dosing regimen where it is required to maintain serum concentrations of the drug within a desired range. Estimation of kinetic parameters for gentamicin in burn patients with normal or only slightly reduced renal function demonstrates a relatively constant distribution volume of 0.25 ± 0.086 liter/kg (mean ±sd)but a relatively variable half-life of 2.1 ± 1.3 hr. This finding supports the view that gentamicin regimens should be individualized even in patients with essentially normal renal function.NIH Grant RR-267 supported our use of the computer within the Health Computer Sciences Facility at the University of Minnesota.