Antiretroviral pharmacology in pregnant women and their newborns

Abstract

The physiologic changes of pregnancy have an impact on antiretroviral pharmacokinetic parameters, but the effect is generally not of sufficient magnitude to warrant alterations in dosing. Although administration of oral zidovudine during labor may not provide equivalent serum drug exposure as with continuous intravenous infusion, the clinical relevance of the difference is unknown. Nevirapine is well absorbed during labor, and sufficient drug for prophylaxis against perinatal transmission crosses the placenta if an oral dose is administered to the mother at least 1 hour before delivery. Placental transfer of reverse transcriptase inhibitors is good, whereas preliminary data suggest that protease inhibitors do not cross the placenta well. The use of antiretrovirals during pregnancy is becoming increasingly common, although their safety, toxicity, and teratogencity in pregnancy have not been well described. Normal growth and development have a profound impact on the pharmacokinetics of antiretrovirals in newborns and infants. Washout elimination of transplacentally acquired drug is slow. The pattern of increase in drug clearance over time will depend on the specific elimination pathway for the agent. Dosing regimens must take into account developmental changes in clearance and appropriate scaling for size. Adherence to antiretroviral regimens is a critical factor in determining the success of prophylactic and therapeutic regimens and is made difficult by the inability of infants to swallow pills and capsules.