Pharmacokinetics of Didanosine in Antepartum and Postpartum Human Immunodeficiency Virus–Infected Pregnant Women and Their Neonates:An AIDS Clinical Trials Group Study

Abstract

Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)-infected women and their neonates were studied. HIV-infected pregnant women received an intravenous (iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m2) was conducted in infants at day 1 and at week 6 after birth. Plasma concentrations of ddI were measured by radioimmunoassay. After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028+/-231 mL/min) versus postpartum (707+/-213 mL/min). No pharmacokinetic parameters after oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy.

Maternal-Fetal Transfer and Amniotic Fluid Accumulation of Nucleoside Analogue Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus-Infected Pregnant Women

“…These data on the NRTIs zidovudine, lamivudine, stavudine, and didanosine show that they cross the placenta in HIVinfected pregnant women, in agreement with previous studies (12,14,15,25,26). Our study includes the first preliminary clinical data available on abacavir, which suggest that its placental transfer is also high.…”

“…For didanosine, the ratio of the concentration in the fetal plasma to that in the maternal plasma was the lowest. Low concentrations of didanosine in the maternal circulation at delivery, largely due to once-a-day dosing, are likely to contribute to the low fetal drug concentrations, which is in accord with experimental findings obtained from animal studies (17), the ex vivo placental perfusion model (6,9), and one clinical trial (25).…”

“…Similar results have been reported with lamivudine (12,14). There have been few clinical studies concerning didanosine or stavudine (25) and no report concerning abacavir.…”

Guidelines for the use of antiretroviral agents in pediatric HIV infection

“…The safety and pharmacokinetics of ddI administered to pregnant women and their neonates have been evaluated in PACTG protocol 249 [174]. A single oral dose of 60 mg/m 2 at 12-24 hours of age and age 6 weeks was studied in the neonates.…”

National Institutes of Health (NIH)

“…The safety and pharmacokinetics of ddI administered to pregnant women and their neonates have been evaluated in PACTG protocol 249 (114). A single oral dose of 60 mg/m 2 at 12-24 hours of age and age six weeks was studied in the neonates.…”