Abstract
The maternal and fetal disposition of 14C-phenytoin (DPH) was evaluated in the pregnant (125-160 days) and non-pregnant baboon. Five pregnant and four non-pregnant female baboons (12-17 kg) were pre-anesthesized with ketamine (7 mg/kg) and maintained under halothane during the first 5 hrs of study. 14C-DPH was administered intravenously as a 5 mg/kg bolus dose and blood, urine and amniotic fluid samples were collected for 48 hours. Results from pharmacokinetic analysis were (mean and SEM).
During the first 5 hrs a significant decrease was observed in the urine output from pregnant animals of the DPH diol and conjugated metabolites (HPPH). In amnionic fluid DPH and HPPH concentrations reached 50% of maternal serum concentration within 24 hrs following DPH administration. At 48 hrs the amnionic/serum ratio for HPPH rose to 0.85 while the DPH ratio remained at 0.50. No other DPH metabolites were observed in the amnionic fluid. It is concluded that during pregnancy DPH conjugation and diol formation are reduced while dist. vol. is increased. The decrease in DPH half-life during pregnancy appears to reflect the increase in dist. vol. rather than changes in clearance (metabolism).
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Raju, T., Paul, L., Beluhan, F. et al. 357 DISPOSITION OF 14C-PHENYTOIN IN THE PREGNANT AND NON-PREGNANT BABOON. Pediatr Res 15 (Suppl 4), 499 (1981). https://doi.org/10.1203/00006450-198104001-00368
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DOI: https://doi.org/10.1203/00006450-198104001-00368