alexa AZT distribution in the fetal and postnatal rat central nervous system.
Infectious Diseases

Infectious Diseases

Journal of AIDS & Clinical Research

Author(s): Busidan Y, Shi X, DowEdwards DL, Busidan Y, Shi X, DowEdwards DL

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Abstract The distribution of 3'-azido-3'-deoxythymidine (AZT, zidovudine), an antiviral drug used in the treatment of human immunodeficiency virus, was investigated in gestation day-20 (G-20) fetuses and in postnatal day-20 (PND-20) rats. At both ages, a single dose of 150 mg/kg (1.78 mmol/kg) AZT was administered orally along with tracer amounts of 14C-AZT, and rats were randomly killed at 15, 30, 60, 120, or 240 min after dosing. The fetuses, brains, and spinal cords were processed for autoradiography. The peak concentrations of AZT in plasma of G-20 and PND-20 rats were 92.2 microg/mL (0.345 micromol/mL) and 56.6 microg/mL (0.21 micromol/mL) at 15 and 30 min after intubation, respectively. The peak concentration of fetal tissue occurred in the colon at 60 min and was 205.8 microg/g tissue. In the G-20 rats, the brain showed higher levels of AZT than spinal cord only at the 30-min sample time, whereas in the PND-20 rats, greater radioactivity was found in the spinal cord up to the 240-min sample time. This pattern of AZT distribution in the central nervous system may hypothetically be attributed to the postnatal development of an organic anion carrier system believed to be responsible for transporting AZT from the brain to the blood, resulting in relatively greater overall exposure of the spinal cord to AZT than observed in the brain. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association
This article was published in J Pharm Sci and referenced in Journal of AIDS & Clinical Research

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