Pharmacokinetic parameters from data relating to the plasma and biliary excretion kinetics of cefmetazole in rats

Abstract

The plasma disposition kinetics and the biliary excretion kinetics of cefmetazole after i.v. administration to rats anaesthetized with pentobarbital sodium were studied. Parametric estimation was carried out using non-linear regression methods with uni- and bivariate analyses. On the basis of statistical criteria a two-compartment model was chosen as the most appropriate for fitting the plasma concentration data, establishing a mean half-life value of the slow disposition phase at around 13 min. Analysis of the plasma and biliary data revealed a mean value for the biliary excretion constant of 0.049 l/min and 0.113 l/min for the urinary excretion constant. The cumulative biliary excretion data showed a mean value of 36.25% of the dose administered. The relationship between the biliary excretion rates and plasma concentrations seems to point to a saturable mechanism of excretion.

Interspecies scaling of biliary excreted drugs

“…25); cefmetazole = 36% in rat as unchanged drug (Ref. 26); Susalimod = ∼90% in animals and 60% humans as unchanged drug (Ref. 8).…”

Effect of Plasma Protein Binding on in Vitro-in Vivo Correlation of Biliary Excretion of Drugs Evaluated by Sandwich-Cultured Rat Hepatocytes

“…Furthermore, the influence of plasma protein binding on the in vitro-in vivo correlation of biliary clearance was assessed. Test compounds such as pravastatin, rosuvastatin, valsartan, cefmetazole, and cefoperazone that were known to be mainly excreted into bile in rats were chosen for the correlation study (Pattinson et al, 1987;García-Agundez et al, 1992;Komai et al, 1992;Nezasa et al, 2002;Yamashiro et al, 2006). for 1 min in supplemented DMEM.…”