Quantitative analysis and pharmacokinetics of reverse transcriptase inhibitors in the pregnant rat
Clark, Teresa Nicole
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For over two decades there has been a ceaseless search for more effective treatments of HIV/AIDS. Today there are a number of different therapies that fall into one of three categories, based on their mechanism of action. All currently marketed anti-HIV drugs are classified as either 1) nucleoside reverse transcriptase inhibitors, 2) non-nucleoside reverse transcriptase inhibitors, or 3) protease inhibitors. Each of these compounds has gone through FDA-regulated clinical trials to prove safety and efficacy. Due to a number of reasons, pregnant women are generally not used during clinical trials, so very little is known about the behavior of drugs during pregnancy. A pregnant rat model has been developed to investigate the pharmacokinetics and placental transport of drugs during pregnancy. Presented here are validated analytical methods for the extraction and quantitation of the nucleoside reverse transcriptase inhibitors azidouridine, didanosine and abacavir in the various matrices needed for maternal-fetal pharmacokinetic studies. Also presented here are the pharmacokinetics of two of these compounds, azidouridine (as compared to zidovudine) and abacavir, using a pregnant rat model.