Effects of Gender, Pregnancy, and Anesthesia on the Pharmacokinetics of Zidovudine in Rats

Abstract

Purpose. The effects of gender, pregnancy and anesthesia on the pharmacokinetics of zidovudine (AZT) were studied in rats.

Methods. Unanesthetized male (MR), female (FR) and pregnant (day 20, PR) rats received 50 mg/kg AZT via a jugular vein cannula. Female (FRA), pregnant (day 20, PRA) and pregnant (day 20, PRR) rats maintained under ketamine: acepromazine: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 lower non-renal clearance in female rats, there were no gender differences in the disposition of AZT. No significant differences were noted in total clearance, non-renal clearance or volume of distribution between 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 removal of fetuses during the experiments did not alter the total clearance of AZT in pregnant rats, however, renal clearance and volume of distribution were decreased by cesarian section.

Conclusions. The rat appears to be a suitable laboratory animal model for investigating AZT disposition during pregnancy. However, results of pharmacokinetic studies when animals are maintained under anesthesia with ketamine :acepromazine:xylazine must be interpreted with caution.

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Correspondence to Stuart Feldman.

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Huang, C.SH., Boudinot, F.D. & Feldman, S. Effects of Gender, Pregnancy, and Anesthesia on the Pharmacokinetics of Zidovudine in Rats. Pharm Res 12, 1647–1651 (1995). https://doi.org/10.1023/A:1016293017318

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  • zidovudine
  • gender
  • anesthesia
  • pregnant
  • pharmacokinetics
  • rats