Skip to main content
NCBI home page
Infectious Diseases in Obstetrics and Gynecology logoLink to Infectious Diseases in Obstetrics and Gynecology
. 1993;1(3):137–143. doi: 10.1155/S1064744993000316

Placental Transport of Zidovudine in the Rhesus Monkey

Louis E Ridgway III 1,2,✉, Thomas S King 1, George I Henderson 1, Steven Schenker 1, Robert S Schenken 1
PMCID: PMC2364303  PMID: 18475334

Abstract

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey.

Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection.

Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection.

Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment.

Full Text

The Full Text of this article is available as a PDF (496.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bashore R. A., Smith F., Schenker S. Placental transfer and disposition of bilirubin in the pregnant monkey. Am J Obstet Gynecol. 1969 Apr 1;103(7):950–958. doi: 10.1016/s0002-9378(16)34445-3. [DOI] [PubMed] [Google Scholar]
  2. Bawdon R. E., Sobhi S., Dax J. The transfer of anti-human immunodeficiency virus nucleoside compounds by the term human placenta. Am J Obstet Gynecol. 1992 Dec;167(6):1570–1574. doi: 10.1016/0002-9378(92)91742-s. [DOI] [PubMed] [Google Scholar]
  3. Centers for Disease Control (CDC) Repeat injuries in an inner city population--Philadelphia, 1987-1988. MMWR Morb Mortal Wkly Rep. 1990 Jan 12;39(1):1–3. [PubMed] [Google Scholar]
  4. Dutton G. J. Developmental aspects of drug conjugation, with special reference to glucuronidation. Annu Rev Pharmacol Toxicol. 1978;18:17–35. doi: 10.1146/annurev.pa.18.040178.000313. [DOI] [PubMed] [Google Scholar]
  5. Good S. S., Reynolds D. J., de Miranda P. Simultaneous quantification of zidovudine and its glucuronide in serum by high-performance liquid chromatography. J Chromatogr. 1988 Sep 23;431(1):123–133. doi: 10.1016/s0378-4347(00)83075-3. [DOI] [PubMed] [Google Scholar]
  6. Hankins G. D., Lowery C. L., Jr, Scott R. T., Morrow W. R., Carey K. D., Leland M. M., Colvin E. V. Transplacental transfer of zidovudine in the near-term pregnant baboon. Am J Obstet Gynecol. 1990 Sep;163(3):728–732. doi: 10.1016/0002-9378(90)91057-j. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Lopez-Anaya A., Unadkat J. D., Schumann L. A., Smith A. L. Pharmacokinetics of zidovudine (azidothymidine). III. Effect of pregnancy. J Acquir Immune Defic Syndr. 1991;4(1):64–68. [PubMed] [Google Scholar]
  10. Minkoff H. L., Moreno J. D. Drug prophylaxis for human immunodeficiency virus-infected pregnant women: ethical considerations. Am J Obstet Gynecol. 1990 Oct;163(4 Pt 1):1111–1114. [PubMed] [Google Scholar]
  11. O'Sullivan M. J., Boyer P. J., Scott G. B., Parks W. P., Weller S., Blum M. R., Balsley J., Bryson Y. J. 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 syndrome clinical trials group study (protocol 082). Zidovudine Collaborative Working Group. Am J Obstet Gynecol. 1993 May;168(5):1510–1516. doi: 10.1016/s0002-9378(11)90791-1. [DOI] [PubMed] [Google Scholar]
  12. SCHENKER S., DAWBER N. H., SCHMID R. BILIRUBIN METABOLISM IN THE FETUS. J Clin Invest. 1964 Jan;43:32–39. doi: 10.1172/JCI104891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]
  15. Watts D. H., Brown Z. A., Tartaglione T., Burchett S. K., Opheim K., Coombs R., Corey L. Pharmacokinetic disposition of zidovudine during pregnancy. J Infect Dis. 1991 Feb;163(2):226–232. doi: 10.1093/infdis/163.2.226. [DOI] [PubMed] [Google Scholar]

Articles from Infectious Diseases in Obstetrics and Gynecology are provided here courtesy of Wiley

RESOURCES