Pharmacokinetic Disposition of Zidovudine during Pregnancy

Abstract

Zidovudine pharmacokinetics was determined in three human immunodeficiency virus type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19 to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured using high-pressure liquid chromatography, and pharmacokinetic analyses were done using model-independent methods. For the pregnant versus postpartum periods, peak zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7 mumol/l versus 4.3 +/- 0.04 mumol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h (P = .41); areas under the concentration curve were 4.5 +/- 1.0 mumol/l x h and 6.8 +/- 0.5 mumol/l x h (P = .02); apparent total body clearances were 2.5 +/- 0.6 l/h/kg and 1.7 +/- 0.4 l/h/kg (P = .05); and apparent steady state volumes of distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively. Umbilical cord serum levels ranged from 113%-127% of maternal levels. No persistent adverse effects of zidovudine therapy were seen in the three women or their babies.

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.…”

“…Zidovudine has been widely used and studied in pregnancy, and high cord-to-maternal plasma drug concentration ratios have been consistently reported (15,26). Similar results have been reported with lamivudine (12,14).…”

Concise overview of the clinical pharmacokinetics of dideoxynucleoside antiretroviral agents

“…It is not yet known whether pregnancy affects the pharmaco kinetics of zidovudine. In one study, an increase in Vss and in zidovudine clearance during pregnancy was explained by the usual increase in body weight, plasma volume and renal and hepatic blood flow seen during pregnancy [21]. The pharmacokinetics of zidovudine were also monitored 3-4 weeks post partum and at that time the pharmacokinetic par ameters were no longer different from those re ported in HIV-infected men.…”

“…Zidovudine distribution into saliva [20] is of particular interest because the ease of collection and avoidance of blood handling could make saliva a favourable matrix for therapeutic drug monitoring. Zidovudine crosses the placenta and has been measured in neonatal blood [21][22][23]. It is not yet known whether pregnancy affects the pharmaco kinetics of zidovudine.…”

Ethical Considerations in Clinical Trials in Asia

“…Although zidovudine did not always prevent vertical transmission of HIV (36), some studies showed that vertical transmission was not observed in a total of 11 cases who had been given zidovudine during pregnancy (37,38). These highly promising data, though preliminary, had been available at the time of protocol development of the PACTG 076 study (39).…”