Lopinavir exposure with an increased dose during pregnancy.
BACKGROUND
Use of standard adult lopinavir/ritonavir (LPV/RTV) dosing (400/100 mg) during the third trimester of pregnancy results in reduced LPV exposure. The goal of this study was to determine LPV exposure during the third trimester of pregnancy and 2 weeks postpartum with a higher LPV/RTV dose.


METHODS
The Pediatric AIDS Clinical Trials Group Protocol 1026s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving LPV/RTV 400/100 mg twice daily during the second trimester and 533/133 mg twice daily during the third trimester through 2 weeks postpartum. Intensive steady state 12-hour pharmacokinetic profiles were performed during the third trimester and at 2 weeks postpartum and were optional during the second trimester. LPV and RTV were measured by reverse-phase high-performance liquid chromatography with a detection limit of 0.09 microg/mL.


RESULTS
Twenty-six HIV-infected pregnant women were studied. Median LPV area under the plasma concentration-time curve (AUCs) for the second trimester, third trimester, and postpartum were 57, 88, and 152 microg.h.mL, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 microg/mL.


CONCLUSIONS
The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 microg.h.mL) in nonpregnant adults taking standard doses. However, the AUC on this increased dose at 2 weeks postpartum was considerably higher. These data suggest that the higher LPV/RTV dose should be used in third trimester pregnant women; that it should be considered in second trimester pregnant women, especially those who are protease inhibitor experienced; and that postpartum LPV/RTV dosing can be reduced to standard dosing by 2 weeks after delivery.
Mirochnick
Mark
M
Department of Pediatrics, Boston University School of Medicine, and Infectious Disease Division, Children's Hospital Boston, Boston, MA 02118, USA. markm@bu.edu
Best
Brookie M
BM
Stek
Alice M
AM
Capparelli
Edmund
E
Hu
Chengcheng
C
Burchett
Sandra K
SK
Holland
Diane T
DT
Smith
Elizabeth
E
Gaddipati
Sreedhar
S
Read
Jennifer S
JS
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D061466:Lopinavir; D011247:Pregnancy / Q000097:blood / Q000378:metabolism*; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir