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. 1995 Feb;39(2):343–345. doi: 10.1128/aac.39.2.343

Effect of zidovudine on transplacental pharmacokinetics of ddI in the pigtailed macaque (Macaca nemestrina).

C M Pereira 1, C Nosbisch 1, W L Baughman 1, J D Unadkat 1
PMCID: PMC162539  PMID: 7726494

Abstract

Since zidovudine and ddI may be used in combination in the future to treat pregnant women who are human immunodeficiency virus positive, we conducted a study to determine whether zidovudine affects the transfer of ddI across the placenta. Zidovudine and ddI were infused simultaneously to three near-term pregnant macaques (Macaca nemestrina) at 156 +/- 1.5 days of gestation. Samples of maternal and fetal blood and amniotic fluid were drawn at intervals for 30 h. The steady-state dideoxyinosine concentrations in the plasma of the dam (Cssd), the fetus (Cssf), and the amniotic fluid (Cssa) and the ratios Cssf/Cssd and Cssa/Cssf were found to be not significantly different from the values previously determined after the administration of ddI alone during the same pregnancy. We conclude that concurrent zidovudine administration does not affect the transfer of ddI across the placenta in near-term Macaca nemestrina.

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Selected References

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  1. Agy M. B., Frumkin L. R., Corey L., Coombs R. W., Wolinsky S. M., Koehler J., Morton W. R., Katze M. G. Infection of Macaca nemestrina by human immunodeficiency virus type-1. Science. 1992 Jul 3;257(5066):103–106. doi: 10.1126/science.1621083. [DOI] [PubMed] [Google Scholar]
  2. Ahluwalia G., Cooney D. A., Mitsuya H., Fridland A., Flora K. P., Hao Z., Dalal M., Broder S., Johns D. G. Initial studies on the cellular pharmacology of 2',3'-dideoxyinosine, an inhibitor of HIV infectivity. Biochem Pharmacol. 1987 Nov 15;36(22):3797–3800. doi: 10.1016/0006-2952(87)90440-0. [DOI] [PubMed] [Google Scholar]
  3. Boudinot F. D., Schinazi R. F., Gallo J. M., McClure H. M., Anderson D. C., Doshi K. J., Kambhampathi P. C., Chu C. K. 3'-Azido-2',3'-dideoxyuridine (AzddU): comparative pharmacokinetics with 3'-azido-3'-deoxythymidine (AZT) in monkeys. AIDS Res Hum Retroviruses. 1990 Feb;6(2):219–228. doi: 10.1089/aid.1990.6.219. [DOI] [PubMed] [Google Scholar]
  4. Collier A. C., Coombs R. W., Fischl M. A., Skolnik P. R., Northfelt D., Boutin P., Hooper C. J., Kaplan L. D., Volberding P. A., Davis L. G. Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection. Ann Intern Med. 1993 Oct 15;119(8):786–793. doi: 10.7326/0003-4819-119-8-199310150-00003. [DOI] [PubMed] [Google Scholar]
  5. Dancis J., Lee J. D., Mendoza S., Liebes L. Transfer and metabolism of dideoxyinosine by the perfused human placenta. J Acquir Immune Defic Syndr. 1993 Jan;6(1):2–6. [PubMed] [Google Scholar]
  6. Gallo J. M., Finco T. S., Swagler A. R., Mehta M. U., Viswanathan C. T., Qian M. Pharmacokinetic evaluation of drug interactions with anti-HIV drugs, II: Effect of 2',3'-dideoxyinosine (ddI) on zidovudine kinetics in monkeys. AIDS Res Hum Retroviruses. 1992 Feb;8(2):277–283. doi: 10.1089/aid.1992.8.277. [DOI] [PubMed] [Google Scholar]
  7. Hartman N. R., Yarchoan R., Pluda J. M., Thomas R. V., Marczyk K. S., Broder S., Johns D. G. Pharmacokinetics of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine in patients with severe human immunodeficiency virus infection. Clin Pharmacol Ther. 1990 May;47(5):647–654. doi: 10.1038/clpt.1990.86. [DOI] [PubMed] [Google Scholar]
  8. Klecker R. W., Jr, Collins J. M., Yarchoan R., Thomas R., Jenkins J. F., Broder S., Myers C. E. Plasma and cerebrospinal fluid pharmacokinetics of 3'-azido-3'-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther. 1987 Apr;41(4):407–412. doi: 10.1038/clpt.1987.49. [DOI] [PubMed] [Google Scholar]
  9. Knupp C. A., Shyu W. C., Dolin R., Valentine F. T., McLaren C., Martin R. R., Pittman K. A., Barbhaiya R. H. Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin Pharmacol Ther. 1991 May;49(5):523–535. doi: 10.1038/clpt.1991.63. [DOI] [PubMed] [Google Scholar]
  10. Liebes L., Mendoza S., Wilson D., Dancis J. Transfer of zidovudine (AZT) by human placenta. J Infect Dis. 1990 Feb;161(2):203–207. doi: 10.1093/infdis/161.2.203. [DOI] [PubMed] [Google Scholar]
  11. Lopez-Anaya A., Unadkat J. D., Schumann L. A., Smith A. L. Pharmacokinetics of zidovudine (azidothymidine). I. Transplacental transfer. J Acquir Immune Defic Syndr. 1990;3(10):959–964. [PubMed] [Google Scholar]
  12. Lopez-Anaya A., Unadkat J. D., Schumann L. A., Smith A. L. Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate. J Acquir Immune Defic Syndr. 1990;3(11):1052–1058. [PubMed] [Google Scholar]
  13. Merigan T. C. Treatment of AIDS with combinations of antiretroviral agents. Am J Med. 1991 Apr 10;90(4A):8S–17S. doi: 10.1016/0002-9343(91)90405-m. [DOI] [PubMed] [Google Scholar]
  14. Ochs H. D., Morton W. R., Tsai C. C., Thouless M. E., Zhu Q., Kuller L. D., Wu Y. P., Benveniste R. E. Maternal-fetal transmission of SIV in macaques: disseminated adenovirus infection in an offspring with congenital SIV infection. J Med Primatol. 1991 Jun;20(4):193–200. [PubMed] [Google Scholar]
  15. Pereira C. M., Nosbisch C., Winter H. R., Baughman W. L., Unadkat J. D. Transplacental pharmacokinetics of dideoxyinosine in pigtailed macaques. Antimicrob Agents Chemother. 1994 Apr;38(4):781–786. doi: 10.1128/aac.38.4.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Qian M. X., Finco T. S., Mehta M., Viswanathan C. T., Gallo J. M. Pharmacokinetic evaluation of drug interactions with zidovudine. I: Probenecid and zidovudine in monkeys. J Pharm Sci. 1991 Nov;80(11):1007–1011. doi: 10.1002/jps.2600801102. [DOI] [PubMed] [Google Scholar]
  17. Ravasco R. J., Unadkat J. D., Tsai C. C., Nosbisch C. Pharmacokinetics of dideoxyinosine in pigtailed macaques (Macaca nemestrina) after intravenous and subcutaneous administration. J Acquir Immune Defic Syndr. 1992 Oct;5(10):1016–1018. [PubMed] [Google Scholar]
  18. Schenker S., Johnson R. F., King T. S., Schenken R. S., Henderson G. I. Azidothymidine (zidovudine) transport by the human placenta. Am J Med Sci. 1990 Jan;299(1):16–20. doi: 10.1097/00000441-199001000-00005. [DOI] [PubMed] [Google Scholar]
  19. Sim S. M., Back D. J., Breckenridge A. M. The effect of various drugs on the glucuronidation of zidovudine (azidothymidine; AZT) by human liver microsomes. Br J Clin Pharmacol. 1991 Jul;32(1):17–21. doi: 10.1111/j.1365-2125.1991.tb05607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tuntland T., Ravasco R. J., al-Habet S., Unadkat J. D. Efflux of zidovudine and 2',3'-dideoxyinosine out of the cerebrospinal fluid when administered alone and in combination to Macaca nemestrina. Pharm Res. 1994 Feb;11(2):312–317. doi: 10.1023/a:1018928013044. [DOI] [PubMed] [Google Scholar]
  21. Wientjes M. G., Au J. L. Lack of pharmacokinetic interaction between intravenous 2',3'-dideoxyinosine and 3'-azido-3'-deoxythymidine in rats. Antimicrob Agents Chemother. 1992 Mar;36(3):665–668. doi: 10.1128/aac.36.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zimmerman T. P., Mahony W. B., Prus K. L. 3'-azido-3'-deoxythymidine. An unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion. J Biol Chem. 1987 Apr 25;262(12):5748–5754. [PubMed] [Google Scholar]

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