The maternal-fetal transfer of 3TC (LAMIVUDINE) in the ex vivo human placenta

OBJECTIVE: 3TC (lamivudine) is currently being used as treatment for hepatitis B and in combination therapies for HIV. We sought to study the transfer of 3TC ((-)-2'-deoxy-3'-thiacytidine) across the human placenta both alone and in the presence of AZT (zidovudine). STUDY DESIGN: Nine placentas from term, elective repeat cesarean deliveries were analyzed using the ex vivo single cotyledon perfusion system. Antipyrine was utilized as the reference compound for the determination of the clearance indices of 3TC alone and in combination with AZT. 3TC and AZT concentrations in the perfusates and tissues were quantified by reverse phase HPLC. RESULTS: The clearance index of 3TC at a maternal concentration of 1.39 ng/mL was 0.23 ±0.14. At a peak concentration of 14.6 ig/mL the CI was 0.14 ±0.06. When the maternal concentration of AZT was 1 ng/mL, the CI of 3TC at the peak and trough concentrations was 0.18 ±0.08 and 0.19 ± 0.10, respectively. When the concentration of AZT was 10 ig/mL the CI of 3TC was 0.15 ±0.07 and 0.17 ±0.09, respectively, for the trough and peak concentrations. In addition, when the perfusion system was closed, there was little accumulation in the fetal perfusate, and in the intervillous space of the placental tissue. CONCLUSION: These data suggest that the CI of 3TC is not altered by the addition of AZT at its peak and trough concentrations. These data also suggest that there is little accumulation of 3TC in the fetal circulation and placental tissue.