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


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.

This is a preview of subscription content, access via your institution.


  1. 1.

    M. S. Gottlieb, R. Schroff, H. M. Schanker, J. D. Weisman, P. T. Fan, R. A. Wolf and A. Saxon. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men, Evidence of a new acquired cellular immunodeficiency. N. Engl. J. Med. 305:1425–1431 (1981).

    Google Scholar 

  2. 2.

    Centers for Disease Control. HIV/AIDS surveillance report. October 1993.

  3. 3.

    L. M. Moffenson, P. F. Wright and P. E. Fast. Summary of the working group on perinatal intervention. AIDS Res. Hum. Retroviruses. 8:1435–1438 (1992).

    Google Scholar 

  4. 4.

    H. D. Langtry and D. M. Campoli-Richards. Zidovidine: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 37:408–450 (1989).

    Google Scholar 

  5. 5.

    A. Ferrazin, A. DeMaria, C. Gotta, G. Mazzarello, A. Canessa, B. Ciravegna, C. Cirillo, F. Melica and A. Terragna. Zidovudine therapy of HIV-1 infection during pregnancy assessment of the effect on the newborns. J. Acquir. Immune. Defic. Syndr. 6:376–379 (1993).

    Google Scholar 

  6. 6.

    R. S. Sperling, P. Stratton, M. J. O'Sullivan, P. Boyer, D. H. Watts, J. S. Lambert, H. Hammill, E. G. Livingston, D. J. Gloeb, H. Minkoff and H. E. Fox. A survey of zidovudine use in pregnant women with human immunodeficiency virus infection. N. Engl. J. Med. 326:857–861 (1992).

    Google Scholar 

  7. 7.

    D. H. Watts, Z. A. Brown, T. Tartaglione, S. K. Burchett, K. Opheim, R. Coombs and L. Corey. Pharmacokinetics disposition of zidovudine during pregnancy. J. Infect. Dis. 163:226–232 (1991).

    Google Scholar 

  8. 8.

    Zidovudine for the prevention of HIV transmission from mother to infant. MMWR 43:285–287 (1994).

  9. 9.

    R. Kato. Sex-related differences in drug metabolism. Drug Metab. Rev. 3:1–32 (1974).

    Google Scholar 

  10. 10.

    P. L. Bonate. Gender-related differences in xenobiotic metabolism. J. Clin. Pharmacol. 31:684–690 (1991).

    Google Scholar 

  11. 11.

    F. E. Hytten and A. M. Thomson. Maternal physiological adjustments. In N. S. Assali (ed.), Biology of Gestation, Academic Press, New York, 1968, pp. 449–479.

    Google Scholar 

  12. 12.

    C. Baylis. Renal hemodynamics and volume control during pregnancy in the rat. Semin. Nephrol. 4:208–220 (1984).

    Google Scholar 

  13. 13.

    A. Lopez-Anaya, J. D. Unadkat, L. A. Schumann and A. L. Smith. Pharmacokinetics of zidovudine (azidothymidine). I. transplacental transfer. J. Acquir. Immune. Defic. Syndr. 3:959–964 (1990).

    Google Scholar 

  14. 14.

    A. Lopez-Anaya, J. D. Unadkat, L. A. Schumann and A. L. Smith. Pharmacokinetics of zidovudine (azidothymidine). III. effect of pregnancy. J. Acquir. Immune. Defic. Syndr. 4:64–68 (1991).

    Google Scholar 

  15. 15.

    G. M. Boike, G. Deppe, J. D. Young, N. L. Gove, S. F. Bottoms, J. M. Malone, Jr., V. K. Malviya and R. J. Sokol. Chemotherapy in a pregnant rat model 1. Mitomycin-C: Pregnancyspecific kinetics and placental transfer. Obstet. Gynecol. 34:187–190 (1989).

    Google Scholar 

  16. 16.

    B. A. Patel, C. K. Chu and F. D. Boudinot. Pharmacokinetics and saturable renal tubular secretion of Zidovudine in rats. J. Pharm. Sci. 78:530–534 (1989).

    Google Scholar 

  17. 17.

    M. Gumbleton, P. J. Nicholls and G. Taylor. Differential influence of laboratory anesthetic regimens upon renal and hepatosplanchnic hemodynamics in the rat. J. Pharm. Pharmacol. 42:693–697 (1990).

    Google Scholar 

  18. 18.

    A. Mercatello. Changes in renal function induced by anesthesia. Ann. Fr. Anesth. Reanim. 9:507–524 (1990).

    Google Scholar 

  19. 19.

    W. J. Jusko. Guidelines for collection and analysis of pharmacokinetic data. In W. E. Evans, J. J. Schentag and W. J. Jusko (eds.), Applied Pharmacokinetics: Principles of therapeutic drug monitoring. Applied Therapeutics, Inc., Vancouver MA, 1992, pp. 19–20.

    Google Scholar 

  20. 20.

    K. Yamaoka, T. Nakagawa and T. Uno. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J. Pharmacokin. Biopharm. 6:165–175 (1978).

    Google Scholar 

  21. 21.

    Statistical Consultants Inc., PCNONLIN and NONLIN 84: Software for the statistical analysis of nonlinear models. Am. Statistician 40:52 (1986).

    Google Scholar 

  22. 22.

    S. S. Good and P. de Miranda. Species differences in the metabolism and disposition of antiviral nucleoside analogues: 2. zidovudine. Antiviral Chem. Chemother. 3:65–77 (1992).

    Google Scholar 

  23. 23.

    I. Muraoka, T. Hasegawa, M. Nadai, K. Kato and T. Nabeshima. Pharmacokinetics and renal handling of enprofylline in pregnant rats. Drug Metab. Dispos. 20:653–657 (1992).

    Google Scholar 

  24. 24.

    M. G. Neale and D. V. Parke. Effects of pregnancy on the metabolism of drugs in the rat and rabbit. Biochem. Pharmac. 22:1451–4161 (1973).

    Google Scholar 

  25. 25.

    M. J. O'Sullivan, P. J. J. Boyer, G. B. Scott, W. P. Parks, S. Weller, M. R. Blum, J. Balsley, Y. J. Bryson and the Zidovudie Collaborative Working Group. The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: Phase I acquired immunodeficiency syndrom clinical trials group study (protocol 082). Am. J. Obstet. Gynecol. 168:1510–1516 (1993).

    Google Scholar 

  26. 26.

    N. H. Booth. Intravenous and other parenteral anesthetics. In N. H. Booth and L. E. McDonald (eds.), Veterinary Pharmacology and Therapeutics, Iowa State University Press, Iowa, 1982, pp. 203.

    Google Scholar 

  27. 27.

    C. J. Green, J. Knight, S. Precious and S. Simpkin. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab. Animal. 15:163–170 (1981).

    Google Scholar 

  28. 28.

    N. S. Lipman, R. P. Marini and S. E. Erdman. A comparison of ketamine/xylazine and ketamine/xylazine/acepromazine anesthesia in the rabbit. Lab. Anim. Sci. 40:395–398 (1990).

    Google Scholar 

  29. 29.

    R. F. Martin. Depressants of the central nervous system; narcotics, anti-convulsant, analgesics. In F. Alexander (ed.) An Introduction to Veterinary Pharmacology. Churchill Livingstone Inc., New York, 1985, pp. 130–155.

    Google Scholar 

  30. 30.

    P. Wang, Z. F. Ba, J. Burkhardt and I. H. Chaudry. Traumahemorrhage and resuscitation in the mouse: effects on cardiac output and organ blood flow. Am. J. Physiol. 264:H1166–1173 (1993).

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Stuart Feldman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

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