Transplacental transfer of zidovudine in the near-term pregnant baboon

Gary Hankins, Curtis L. Lowery, Richard T. Scott, W. Robert Morrow, K. D. Carey, M. Michelle Leland, Edward V. Colvin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Approximately one third of infants born to human immunodeficiency virus type 1 seropositive mothers have evidence of infection or of acquired immunodeficiency syndrome by the age of 18 months. One fifth of infected infants also have died by age 19 months. This prevalence, combined with the demonstration that zidovudine (formerly azidothymidine) can decrease mortality and the frequency of opportunistic infections in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex, may lead to increasing use of azidothymidine in pregnancy despite a paucity of information regarding its pharmacokinetics. To further investigate the distribution of azidothymidine and its inactive metabolite 5′-glucuronide azidothymidine in the mother, fetus, and amniotic fluid, 12 near-term pregnant baboons were given oral azidothymidine (21 mg/kg/day in four divided doses every 6 hours, equivalent to the usual nonpregnant human dose of 1500 mg/day). Specimens of maternal blood, fetal arterial blood obtained by percutaneous umbilical cord blood sampling, and amniotic fluid were obtained after from one to 17 doses of azidothymidine. Azidothymidine levels were measured by radioimmunoassay with the INCSTAR commercial radioimmunoassay kit and using Escherichia coll β-glucuronidase for determination of 5′-glucuronide azidothymidine levels. Paired analyses revealed significant concentration gradients between amniotic fluid, fetal serum, and maternal serum for both azidothymidine (p < 0.019) and 5′-glucuronide azidothymidine (p < 0.002). The amniotic fluid 5′-glucuronide azidothymidine level increased with increasing doses of azidothymidine despite the fact that the maternal azidothymidine and 5′-glucuronide azidothymidine concentrations were unchanged. This accumulation of amniotic fluid 5′-glucuronide azidothymidine may provide a functional drug reservoir and contribute to the higher fetal concentrations of the medication and its metabolite. Alternatively, the higher fetal levels may represent slower clearance in the fetus than in the mother. Further studies appear warranted with respect to possible adverse fetal effects, especially bone marrow suppression with prolonged and chronic exposure to azidothymidine.

Original languageEnglish (US)
Pages (from-to)728-732
Number of pages5
JournalAmerican Journal of Obstetrics and Gynecology
Volume163
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

Zidovudine
Papio
Glucuronides
Amniotic Fluid
Mothers
Cordocentesis
Acquired Immunodeficiency Syndrome
Fetal Blood
Radioimmunoassay
Fetus
Escherichia
Glucuronidase
Opportunistic Infections
Serum

Keywords

  • acquired immunodeficiency syndrome
  • Azidothymidine
  • placental transfer

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Hankins, G., Lowery, C. L., Scott, R. T., Morrow, W. R., Carey, K. D., Leland, M. M., & Colvin, E. V. (1990). Transplacental transfer of zidovudine in the near-term pregnant baboon. American Journal of Obstetrics and Gynecology, 163(3), 728-732. https://doi.org/10.1016/0002-9378(90)91057-J

Transplacental transfer of zidovudine in the near-term pregnant baboon. / Hankins, Gary; Lowery, Curtis L.; Scott, Richard T.; Morrow, W. Robert; Carey, K. D.; Leland, M. Michelle; Colvin, Edward V.

In: American Journal of Obstetrics and Gynecology, Vol. 163, No. 3, 1990, p. 728-732.

Research output: Contribution to journalArticle

Hankins, G, Lowery, CL, Scott, RT, Morrow, WR, Carey, KD, Leland, MM & Colvin, EV 1990, 'Transplacental transfer of zidovudine in the near-term pregnant baboon', American Journal of Obstetrics and Gynecology, vol. 163, no. 3, pp. 728-732. https://doi.org/10.1016/0002-9378(90)91057-J
Hankins, Gary ; Lowery, Curtis L. ; Scott, Richard T. ; Morrow, W. Robert ; Carey, K. D. ; Leland, M. Michelle ; Colvin, Edward V. / Transplacental transfer of zidovudine in the near-term pregnant baboon. In: American Journal of Obstetrics and Gynecology. 1990 ; Vol. 163, No. 3. pp. 728-732.
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