Quantitative analysis and pharmacokinetics of antiviral agents in the pregnant rat
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Antiviral drugs are used therapeutically in pregnancy for treatment of both mother and fetus. Antiviral drugs are presumed to prevent viral transmission from mother to fetus by decreasing maternal viral load and/or accumulation of the drugs in the fetal compartment. Due to a number of reasons, pregnant women are generally not used during clinical trials, so very little is known about the behavior of therapeutic agents during pregnancy. A pregnant rat model has been developed to investigate the pharmacokinetics and placental transport of antivirals during pregnancy. Presented here are validated analytical methods for the extraction and quantitation of the nucleoside reverse transcriptase inhibitors zalcitabine (DDC) and stavudine (D4T) in the various matrices needed to support the maternal-fetal pharmacokinetic studies. Also presented here are the pharmacokinetics of DDC and D4T, using the pregnant rat model.