The pharmacokinet1cs of 3tc administered to HIV-1 infected women (pre-partum, during labour and post-partum) and their offspring

Objectives: Recently published data has shown that Retrovir given in pregnancy during delivery, and to the neonate can substantially reduce the transmission of HIV infection from 25.5% (placebo) to 8.3% [Connor EM e al 1994]. Combination of lamivudine (3TC) and Retrovir; have demonstrated a greater effect on viral load and immunological markers than either drug as monotherapy. Methods: This study was designed to investigate the safety and pharmacokinetics of 3TC atone (300mg bid ie. about 8mg/kg/day) and in combination with Retrovir (150mg bid 3TC. 300mg bid Retrovir), when given orally to pregnant women from week 38 of pregnancy, through labour and up to I week post-birth. All neonates were dosed orally with 3TC atone (8mg/kg/day) or in combination with Retrovir (8mg/kg/day) depending on what their mother received during pregnancy. Dosing of the neonates began 12 hours post-birth and continued (bid) for I week. Samples of Wood, amniotic fluid, vaginal secretions and breast rritk were taken as appropriate. Results: Preliminary pharmacokinetic data are available from thirteen mothers and their neonates (birthweight 27-3.7kg).The parameters of Clo, Cmax AUC, tmax and t in pregnant women are similar to those obtained in non-pregnant adults and exhibit proportionality between tow and high 3TC doses. 3TC freely crossed the placenta as the serum concentrations at birth in mother; umbilical cord and neonate are very similar Following birth, maternal 3TC pharmacokinetics do not appear different from non-pregnant adults. Neonates have immature organ function at birth, but the kidneys attain moderate function relatively quickly. After I week of dosing, the clearance of 3TC in neonates is less than that seen in paediatric patients at the same dose level (Q/F estimates are 0.35 L/h/kg and 1.1 L/hAg for neonates and paediatrics (<2yrs) respectively). Cmax values are consistent wrth those seen previously in paediatrics at this dose tevd (1-2ug/ml) and overall exposure (as AUQ is within that previously observed (12h.ug/mL) in paediatrics. Conclusion: There have been no adverse clinical effects. The pharmacokinetic data at present indicate that the recommended adurt combination dose for 3TC ( 150mg bid) should be maintained in pregnant women but the paediatric dose of 8mg/kg/day should be reduced in neonates to 4mg/kg/day (divided as appropriate).