COMPARATIVE STUDY
JOURNAL ARTICLE
MULTICENTER STUDY

Reduced lopinavir exposure during pregnancy

Alice M Stek, Mark Mirochnick, Edmund Capparelli, Brookie M Best, Chengcheng Hu, Sandra K Burchett, Carol Elgie, Diane T Holland, Elizabeth Smith, Ruth Tuomala, Amanda Cotter, Jennifer S Read
AIDS 2006 October 3, 20 (15): 1931-9
16988514

BACKGROUND: Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy.

METHODS: We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was > or = 52 microg h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 microg h/ml).

RESULTS: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 microg h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C12h) was 1.6 microg/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 microg h/ml (90% CI, 49.7-85.4) and C12h was 4.6 microg/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13.

CONCLUSIONS: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
16988514
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"