Abstract
A study from Rolf van Heeswijk and colleagues from the Ottawa Health Research Institute in Canada evaluated the pharmacokinetics and its active metabolite M8 during pregnancy and post partum.
A group of 11 women receiving 1,250 mg BID of nelfinavir and two nucleosides were assessed in this longitudinal study. Twelve hour nelfinavir and M8 levels were analysed by LC/MS/MS at a median of 33 weeks during the third trimester and a second analysis was performed post partum at a median of eight weeks following the first sampling.
The investigators reported the post partum geometric mean nelfinavir AUC 0-12h, Cmax and C12h to be 31.0 h mg/L, 4.84 mg/L and 1.21 mg/L respectively (comparable with population values). The geometric mean ratio (GMR) third trimester/post partum (90% CI) for nelfinavir AUC 0-12h, Cmax and C12h was 0.76 (0.54–1.06), 0.81 (0.57–1.15) and 0.43 (0.25–0.76) respectively.
For the M8 AUC 0-12h, Cmax and C12h GMR (90% CI) was 0.32 (0.18-0.55), 0.31 (0.19-0.51), and 0.30 (0.14-0.64) respectively. The median ration of the AUC 0-12h of M8 and NFV during the third trimester and post partum was 11% and 27% respectively and the GMR and 90% CI was 0.42 (0.33–0.53).
The investigators noted a trend towards reduced exposure to nelfinavir during pregnancy (AUC reduced by 24%) that they suggest is due to induction of CYP3A4 and/or CYP2D6. They also reported significant reductions in concentrations of the active metabolite M8 (reduced by 70%) during pregnancy, which may be due to induction of CYP3A4 and/or inhibition of CYP2C19 and the clinical implications of which are unclear.
All women in this study maintained an undetectable plasma viral load and a stable CD4 cell count during pregnancy and post partum.