Nevirapine Pharmacokinetics in Pregnant Women and in Their Infants After in Utero Exposure

Abstract

The safety, toxicity and pharmacokinetics of nevirapine were studied in HIV-infected pregnant women beginning chronic therapy late in the third trimester and in their infants. Initial dose pharmacokinetic profiles in the pregnant women were similar to those seen in nonpregnant adults. Serum nevirapine concentrations fell below the 100-ng/ml target concentration by Day 7 of life in four infants, suggesting that nevirapine elimination is accelerated in these infants compared with newborns whose mothers receive only a single intrapartum nevirapine dose.

Implications of gender and pregnancy for antiretroviral drug dosing

“…Pharmacokinetics of single-dose nevirapine in late pregnancy before labor onset are equivalent to those seen in nonpregnant adults [46]. When single doses are administered during labor, however, the pharmacokinetics of nevirapine are significantly different, with increased oral clearance, half-life, and apparent volume of distribution, and decreases in AUC and maximum concentration [46][47][48].…”

“…When single doses are administered during labor, however, the pharmacokinetics of nevirapine are significantly different, with increased oral clearance, half-life, and apparent volume of distribution, and decreases in AUC and maximum concentration [46][47][48]. Nevirapine crosses the placenta rapidly and effectively.…”

11.0 References

“…Despite the welldocumented cutaneous, mucosal and hepatotoxicity with nevirapine at higher CD4 T-lymphocyte counts, nevirapine remains an option for women with a CD4 T-lymphocyte count <250 cells/mL. Nevirapine is well tolerated in pregnancy, with several studies suggesting this to be the case even above the stated CD4 cell count cut-off [68][69][70][71]; has favourable pharmacokinetics in pregnancy [72][73][74] and has been shown to reduce the risk of MTCT even when given as a single dose in labour, alone or supplementing zidovudine monotherapy or dual therapy [75][76][77].…”

“…Among the NNRTIs, nevirapine has been extensively studied in pregnancy and plasma concentrations are similar to those in non-pregnant adults [72,74]. No dose adjustment is required when using licensed doses.…”

Guidelines for the use of antiretroviral agents in pediatric HIV infection

“…However, multidose NVP pharmacokinetics have been evaluated in children as young as 2 months; in the youngest children, clearance was lower than in older children but greater than in adults, suggesting rapid maturation of NVP metabolism during the first 2 months of life [179]. A study of pharmacokinetics of the single NVP dose in 10 infants born to infected mothers who have received multiple NVP doses (as opposed to a single dose) during pregnancy indicated that a single infant NVP dose of 2 mg/kg orally at age 48-72 hours did not maintain NVP concentrations above the desired 100 ng/mL through age 7 days in 4 of 10 infants, suggesting possible in utero induction of NVP metabolic enzymes in the fetal liver, and that NVP may need to be given more than once during the first week of life to maintain virucidal levels when the mother has received NVP treatment during pregnancy [180]. The NVP dose for infected infants aged 15 days to 3 months is under study in a phase II clinical trial, PACTG protocol 356.…”