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Systemic Pharmacokinetics (PK) of Oral Zidovudine (ZDV) Given during Labor and Delivery to HIV-1-Infected Pregnant Women A. DORENBAUM1, J. H. RODMAN2, M. MIROCHNICK3, J HERNANDEZ4, A. FRIDLAND2, and ACTG 324 Team5. 1Univ. California, San Francisco; 2St. Jude Children's Res. Hosp., Memphis TN; 3Boston Univ., MA; 4 Glaxo Wellcome Inc., Res. Triangle Park, NC; and 5Pediatric AIDS Clin. Trials Group Intrapartum administration of ZDV by intravenous infusion, as used in ACTG 076, is not practical worldwide. It is not known whether administration of oral ZDV during labor provides equivalent drug exposure for protection against HIV transmission. We examined the tolerance and PK of oral ZDV to determine the feasibility of a more easily administered regimen than the current IV intrapartum regimen recommended based on ACTG 076. METHODS: ZDV concentrations were determined after giving 300 mg oral doses q 3H beginning at the onset of labor in 5 HIV-1 infected women. Blood samples were obtained before and 0.5, 1.0, 1.5, 2, and 3 H after the 1st (D1) and 3rd (D3)doses. RESULTS: Mean (range) Cmax was 0.83 (0.3-1.39) mg/l after D1 and 0.96 (0.44 - 1.41) mg/l after D3, while Cmin values were 0.1 (0.05-0.18) mg/l for D1 and 0.14 (0.08-0.23) mg/l for D3. Median concentrations were less than 0.5 mg/l at all time points except for 0.5 and 1.0 H after D3 and consistently lower than predicted for similar doses in non-pregnant adults and women studied during the third trimester of pregnancy. Additionally, the median concentrations in this study were lower than the median of 0.53 mg/l found in ACTG 296 that included the recommended IV ZDV infusion. In this study, oral ZDV was well tolerated during labor. CONCLUSIONS: The lower than anticipated ZDV plasma concentrations with oral administration may be due to either decreased absorption or higher systemic clearence. Based on these initial results, in developed countries, it is advisable to continue to use IV ZDV during active labor. We are investigating a regimen consisting of a loading dose of 600 mg followed by 300 mg q3 H. This revised regimen should provide concentrations comparable to those obtained with the IV ZDV infusion. Key Words: Perinatal, Transmission, Zidovudine |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |