Effect of benzylpenicillin on the disposition of cefodizime in rats: no net effect on total clearance due to decreased hepatobiliary clearance and increased renal clearance. 
Effect of benzylpenicillin (PCG) on the disposition of [14C]cefodizime (CDZM), a nonmetabolizable analog of cefotaxime, was studied in rats.  Rats were divided into two groups to receive i.v.  injection of [14C]CDZM (15 mg/kg) alone and during the infusion of PCG.  Although the total concentration of [14C]CDZM in plasma vs. time data were almost the same between the groups, the unbound concentration of [14C]CDZM was increased 2-fold by the treatment with PCG.  Hepatobiliary excretion of [14C]CDZM was reduced by the treatment with PCG, indicating that PCG inhibits the transport of CDZM across the sinusoidal and/or bile canalicular membrane(s).  Further support for this hypothesis is the finding that the uptake of [14C]CDZM by the isolated hepatocytes in vitro was via an active transport process that was reduced by PCG.  Furthermore, pharmacokinetic analysis of the data obtained from in vivo and in vitro experiments indicated that PCG reduced the permeability of [14C]CDZM across the sinusoidal and bile canalicular membranes to 32% and 40% of the control value, respectively.  The urinary excretion of [14C]CDZM was principally via the glomerular filtration process and was not affected by the treatment with PCG.  Because of the 2-fold rise in the unbound fraction of [14C]CDZM in the treated rats, the renal clearance for total [14C]CDZM was increased 2-fold by the treatment with PCG.  The increase in the renal clearance compensated for the decrease in the hepatic clearance.  The net effect of the alterations in these pharmacokinetic parameters resulted in no change in the time profiles of [14C]CDZM concentration in plasma between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)