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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 18 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 coli beta-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 less than 0.019) and 5'-glucuronide azidothymidine (p less than 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.
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
February 1996,
Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
January 1990,
Journal of acquired immune deficiency syndromes,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
July 1998,
Pediatric research,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
December 2010,
British journal of pharmacology,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
October 2022,
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
September 2003,
Veterinary journal (London, England : 1997),
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
April 1998,
Bulletin of environmental contamination and toxicology,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
December 1998,
Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
January 1993,
Drug metabolism and disposition: the biological fate of chemicals,
G D Hankins, and
C L Lowery, and
R T Scott, and
W R Morrow, and
K D Carey, and
M M Leland, and
E V Colvin
May 1997,
American journal of obstetrics and gynecology,
