The steady-state pharmacokinetics (PK) of nelfinavir (NFV) and M8 during pregnancy and postpartum
van Heeswijk, R.P.G., Kahliq, Y., Gallicano, K., Bourbeau, M., Seguin, I., Phillips, E. and Cameron, B. (2004) The steady-state pharmacokinetics (PK) of nelfinavir (NFV) and M8 during pregnancy and postpartum. In: 5th International Workshop on Clinical Pharmacology of HIV Therapy, 1 - 3 April 2004, Rome, Italy.
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.
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