Reduced lopinavir exposure during pregnancy.
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.
Stek
Alice M
AM
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA, USA. stek@usc.edu
Mirochnick
Mark
M
Capparelli
Edmund
E
Best
Brookie M
BM
Hu
Chengcheng
C
Burchett
Sandra K
SK
Elgie
Carol
C
Holland
Diane T
DT
Smith
Elizabeth
E
Tuomala
Ruth
R
Cotter
Amanda
A
Read
Jennifer S
JS
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011645:Puerperal Infection / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir