Temocillin pharmacokinetics in normal and impaired renal function

In 18 healthy volunteers and 18 patients with varying degrees of impaired renal function, the plasma concentrations after intravenous administration of temocillin 0.5, 1, and 2g were determined. Another group of 6 patients received temocillin 0.5 g intramuscularly. Surprisingly, it was found that with higher doses, the plasma concentrations, and consequently the area under the plasma concentration/time curve (AUC), did not increase proportionately. Instead, the renal and, to a greater extent, the total clearance of temocillin increased. The plasma concentrations in patients with impaired renal function were clearly higher than in the subjects with normal renal function. Dose-reduction factors were derived which allowed the determination of the dosing regimen necessary to achieve approximately the same high plasma concentrations (and the same AUCs) in patients with impaired renal function as in healthy subjects. However, these dose-reduction factors could only be determined for certain doses because of the specific behaviour of temocillin.