EFFECTS OF GENDER, PREGNANCY, AND ANESTHESIA ON THE PHARMACOKINETICS OF ZIDOVUDINE IN RATS

Purpose. The effects of gender, pregnancy and anesthesia on the pharma cokinetics of zidovudine (AZT) were studied in rats. Methods. Unanesth etized male (MR), female (FR) and pregnant (day 20, PR) rats received 50 mg/kg AZT via a jugular vein cannula. Female (FRA), pregnant (day 2 0, PRA) and pregnant (day 20, PRR) rats maintained under ketamine: ace promazine:xylazine anesthesia also received 50 mg/kg AZT. Two fetuses were removed at each sampling time from the PRR group. Plasma samples were collected and analyzed by RIA. Results. With the exception of a l ower non-renal clearance in female rats, there were no gender differen ces in the disposition of AZT. No significant differences were noted i n total clearance, non-renal clearance or volume of distribution betwe en pregnant and female rats, however, significant differences in renal clearance values were evident. Anesthesia resulted in decreased total , renal and non-renal clearances in female and pregnant rats. The remo val of fetuses during the experiments did not alter the total clearanc e of AZT in pregnant rats, however, renal clearance and volume of dist ribution were decreased by cesarian section. Conclusions. The rat appe ars to be a suitable laboratory animal model for investigating AZT dis position during pregnancy. However, results of pharmacokinetic studies when animals are maintained under anesthesia with ketamine:acepromazi ne:xylazine must be interpreted with caution.