Tenofovir population pharmacokinetics in pregnancy

Changes in tenofovir pharmacokinetics (PK) during pregnancy are associated with weight gain and reduction in serum creatinine with enhanced glomerular filtration, according to an analysis presented at the 14th International Pharmacology Workshop.

Physiological changes that occur during pregnancy, including altered gastrointestinal function and increased glomerular filtration rate, have the potential to alter drug disposition. An approximate reduction of one third in tenofovir exposure during pregnancy has previously been observed in other studies.

IMPAACT P1026 is an ongoing, prospective, non-blinded study of PK in pregnant women receiving routine antiretroviral treatment (ART). This analysis included data from women receiving 300 mg tenofovir disoproxil fumarate (135.6 mg tenofovir), either as a standalone in an ART regimen or as a component of a fixed dose combination.

The investigators collected steady state tenofovir PK profiles in the third trimester – at 30 to 36 weeks gestation – and two to 12 weeks post partum. There was also optional sampling in the second trimester – between 20 and 26 weeks gestation.

Samples were taken pre-dose and 1, 2, 4, 6, 8, 12 and 24 hours post-dose. Tenofovir plasma concentrations were determined by LC-MS-MS.

Pregnancy stage, serum creatinine, concomitant antiretrovirals (ritonavir boosted PIs), albumin and age were assessed as potential covariates in univariate and multivariate models.

The 86 steady-state PK profiles collected included 650 plasma tenofovir concentrations from 46 women during the second trimester (n=7), third trimester (n=41) and postpartum (n=38); 54 (63%) women received a boosted PI.

The investigators found age, pregnancy state, serum creatinine and age to be associated with CL/F in univariate analysis but only serum creatinine remained significant in the multivariate model.

Post hoc AUC estimates were significantly lower during the third trimester vs postpartum: GM 2.38 vs 2.90 mcg*h/mL, p=0.009 with a third trimester ratio of 0.83 (90% CI 0.75 – 0.91).

Powell MB et al. Changes in tenofovir population pharmacokinetics during pregnancy. 14th International Workshop on Clinical Pharmacology. 22-24 April 2013. Amsterdam. Poster abstract PP_03.