PHARMACOKINETICS OF CEFAMANDOLE IN RABBITS WITH EXPERIMENTALLY INDUCED RENAL IMPAIRMENT

Abstract

The pharmacokinetics of cefamandole have been studied in rabbits with normal renal function and varying degrees of renal impairment caused experimentally, by uranyl nitrate, after i.v. administration of a single dose of 30 mg/kg of the antibiotic. The plasma concentrations of cefamandole 80 minutes after administration were 3 μg/ml in normal rabbits reaching 90 μg/ml at 9 hours in the case of terminal renal impairment. With respect to the pharmacokinetic parameters established in rabbits with normal renal function, the following modifications may be observed in the case of rabbits with renal impairment: α, β, K₁₂, K₂₁, K₁₃, V_c and V_p are decreased, while there is an increase in t_1/2α, t _1/2β and (AUC) ^∞₀. inear relationships have been established between log α and log β, respectively, and serum creatinine. Biliary excretion of cefamandole is increased parallel to the increase in the degree of renal impairment, there being a linear relationship between the percentage excreted of the antibiotic and serum creatinine. The values of K_B fall from 0.57 h-¹ in rabbits with normal renal function, to 0.26 h-¹ in rabbits with severe renal impairment.