1994 Volume 42 Issue Supplement4 Pages 251-267
The pharmacokinetics of biapenem (BIPM), a new parenteral antibiotic, following single or multiple intravenous administration was studied in rats using [14C] BIPM.
Plasma concentration of radioactivity intravenously administered decreased in the biexponential pattern. Co and AUC values increased proportionally to administered doses, and T1/2 a values (0.3hr) were equal irrespective of doses of 5 to 50mg/kg. These results suggest that the plasma concentration of [14C] BIPM shows a linear pharmacokinetic nature in rats.
[14C] BIPM was rapidly distributed to diverse tissues. The higher levels of tissue radioactivity were observed in kidney and urinary bladder, and brain and spinal cord were very low. Immediately after the i. v. injection of [14C] BIPM, the radioactivity declined rapidly in all tissues except for kidney as an excretory organ. Tissue distribution of [14C] BIPM in female rats showed similarity to that in main tissues of male rats. The autoradiogram showed that the radioactivity was rapidly distributed to the whole body but no radioactivity was detected in the brain and spinal cord.
After administration of rci BIPM to pregnant rats, high levels of radioactivities were observed in uterus and placenta, whereas very low levels in fetus and amniotic fluid. These distribution patterns in pregnant rats were compatible with the autoradiogrms of pregnant rats.
Milk concentration of radioactivity showed relatively higher levels than that in blood at 1 hour and later after administration. Twenty-four hours after administration, however, the milk levels of the radioactivity became below the detection limit.
[14C] BIPM was rapidly eliminated mainly through the kidney and slightly through the hepatic (biliary) route. Approximately 94% of the administered radioactivity was excreted into urine, and the fecal excretion was below 0.2% of the dose during the first 8 hours in rats.
The amount of metabolites after administration ofc4ciBIPM was small, and two major metabolites were detected in rat plasma and urine.
The concentration of radioactivity in each organ after 10th administration slightly increased, but none of accumulation was specified in any organs. Cumulative excretion of radioactivity in urine and feces was 98% of total dose by 7 days after 10th administration and 95% of radioactivity was excreted in the urine.
In renal dysfunction rats, the decreasing rate of the plasma concentration of radioactivity was delayed and urinary excretion was lowered in parallel with lowering of creatinine clearance (Ccr).
