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.

Population Pharmacokinetics of Emtricitabine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Neonates

“…FTC is primarily excreted by the kidney by both glomerular filtration and tubular secretion, with 86% recovery of the dose achieved in urine, as described in the full prescribing information for Truvada (http://www.gilead.com/pdf/truvada_pi.pdf). During pregnancy, renal plasma flow increases by 25 to 50% and glomerular filtration rate by 50%, which should have enhanced FTC elimination (13). The lowest FTC clearance increase in the PATCG/ IMPAACT P1026 study (23.3 liters/h versus 28.0 liters/h in our study) may be due the sampling time during pregnancy (third trimester versus the day of delivery in our study).…”

Pregnancy-Related Effects on Nelfinavir-M8 Pharmacokinetics: a Population Study with 133 Women

“…Marzolini et al (16) also noted that maternal concentrations of protease inhibitors and nevirapine measured at delivery were lower than those observed in a general HIV-infected population and suggested that the decrease in plasma levels resulted from the nonspecific stimulation of general metabolism and enzyme expression level. Mirochnick et al (18) reported that women in labor given nevirapine demonstrated an increase in nevirapine halflife and a decrease in bioavailability. In our study, low nelfinavir and M8 concentrations at delivery could be explained by a decrease in bioavailability.…”

Antiretroviral treatment during pregnancy

“…In general, plasma drug levels are lower during pregnancy than postpartum [8][9][10][11][12][13][14]. However, it is unclear whether lower concentrations induce virologic failure, increase MTCT, or cause more frequent treatment changes.…”