Abstract
The biliary excretion of [14C]phenytoin (DPH) was examined in pregnant and nonpregnant female control rats. After administration of [14C]DPH (1 mg/kg i.v.), the bile concentration (nanomoles per milliliter) and biliary excretion (nanomoles per minute per kilogram) of the glucuronide conjugate of the major primary metabolite of DPH, 5-phenyl-5-p-hydroxyphenyl[4-14C] hydantoin ([14C)]HPPH), was significantly decreased at 15 and 30 min in pregnant rats relative to controls. Bile flow averaged 50 and 70 microliter/min/kg in control and pregnant rats, respectively. The concentration in blood of [14C]HPPH-glucuronide was increased 2 to 6-fold in pregnant rats relative to controls. After administration of [14C]HPPH (10 mg/kg i.v.), the disappearance of [14C]HPPH from the blood, biliary excretion and bile concentration of [14C]HPPH-glucuronide were very similar in control and pregnant rats. The blood concentration of [14C]HPPH-glucuronide was elevated 2 to 6-fold in pregnant rats and the half-life was increased from 43 min in controls to 70 min in pregnant rats. Maximal bile/blood concentration ratios of [14C]HPPH-glucuronide were 630 and 300 in control and pregnant rats, respectively, indicating a decreased ability of the liver to concentrate the glucuronide in the bile in pregnancy.
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The effect of pregnancy on the biliary excretion of [14C]phenytoin in the rat.
