Pharmacokinetics of Ampicillin Trihydrate, Sodium Ampicillin, and Sodium Dicloxacillin following Intramuscular Injection

Abstract

Serum levels of penicillin activity were determined following intramuscular administration to humans of sodium ampicillin solution, three ampicillin trihydrate suspensions, and sodium dicloxacillin solution. The rates of absorption of the drugs from the intramuscular injection sites were calculated using the method of Wagner and Nelson, with and without intravenously determined elimination constants, and the method of Loo and Riegelman. The ampicillin suspension and dicloxacillin solution data exemplified the interesting pharmacokinetic case in which the absorption process is slower than the elimination process. In this situation, the descending portion of the serum curve reflects the absorption process rather than the elimination process. Calculations confirmed that intravenous data were required to differentiate these processes under these conditions. Ampicillin solution data followed the usual pattern where the descending portion of the serum curve reflects the elimination process. Serum level curves were displayed by an analog computer programmed with a two-compartment open model, and the rate constants were calculated by the Loo-Riegelman method. The computer-generated lines agreed with the experimental data except for the early times following the ampicillin trihydrate suspensions. When the computer was programmed with a kinetic model that depicted absorption as two successive first-order steps, however, the computer lines agreed with the experimental data at all times.