Pharmacokinetics of zidovudine and lamivudine in neonates following coadministration of oral doses every 12 hours

A phase I, repeat-dose, open-label study was conducted to determine the pha rmacokinetics and safety of zidovudine and lamivudine, coadministered orall y every 12 hours, in 16 neonates whose mothers were infected with human imm unodeficiency virus type I (HIV-1). The prospective mothers had been stabil ized on a zidovudine/lamivudine regimen since week 36 of pregnancy to preve nt mother-to-child transmission of HIV. During 3 week postpartum, the mothe rs received zidovudine 300 mg plus lamivudine 150 mg every 12 hours and bre astfed. Neonatal treatment was initiated 12 hours following birth with 4 mg /kg of zidovudine suspension plus 2 mg/kg of lamivudine solution every 12 h ours; this regimen was continued for 1 week. Between days I and 7 of neonat al treatment, the neonatal oral clearance (CL/F) of zidovudine and lamivudi ne increased by 2-fold (p < 0.001) and 1.6-fold (p = 0.004), respectively, possibly reflecting maturation of intestinal hepatic and renal function occ urring during the first week of life. Day 7/day I ratios for exposure (area under the serum concentration-time curve [AUC]) and maximum observed serum concentration (C-max) were 0.48 and 0.63, respectively, for zidovudine and 0.64 and 0.73, respectively, for lamivudine. At the time of delivery, the geometric mean cord/maternal concentration ratio was 1.24 for zidovudine an d 1.12 for lamivudine, indicating free passage of each drug across the plac enta. The maternal and neonatal treatment regimens were well tolerated. The results of this study confirm that in the neonate, a convenient regimen co mbining zidovudine 4 mg/kg and lamivudine 2 mg/kg, administered orally ever y 12 hours, provides zidovudine serum exposure very similar to that reporte d with the standard neonatal zidovudine regimen of 2 mg/kg every 6 hours, a s well as lamivudine serum exposure within the range reported in adults rec eiving lamivudine 150 mg twice a day and children receiving 4 mg/kg twice a day.