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Lopinavir Exposure With an Increased Dose During Pregnancy

Mirochnick, Mark MD*; Best, Brookie M PharmD; Stek, Alice M MD; Capparelli, Edmund PharmD; Hu, Chengcheng PhD§; Burchett, Sandra K MD; Holland, Diane T DPhil; Smith, Elizabeth MD; Gaddipati, Sreedhar MD#; Read, Jennifer S MD**for the PACTG 1026s Study Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 2008 - Volume 49 - Issue 5 - p 485-491
doi: 10.1097/QAI.0b013e318186edd0
Clinical Science

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 μg/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 μg·h−1·mL−1, respectively. Median minimum LPV concentrations were 1.9, 4.1, and 8.3 μg/mL.

Conclusions: The higher LPV/RTV dose (533/133 mg) provided LPV exposure during the third trimester similar to the median AUC (80 μg·h−1·mL−1) 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.

From the *Department of Pediatrics, Boston University School of Medicine, Boston, MA; †University of California, San Diego Schools of Medicine and Pharmacy and Pharmaceutical Sciences, San Diego, CA; ‡Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA; §Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA; ‖Infectious Disease Division, Children's Hospital Boston, Boston, MA; ¶National Institute of Allergy and Infectious Diseases, Bethesda, MD; #Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY; and **Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

Received for publication March 26, 2008; accepted July 11, 2008.

Supported in part by the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases (Grants U01 AI04189, U01 AI41089, UO1 AI27560-18, and U01 AI32907), the General Clinical Research Center Units funded by the National Center for Research Resources (Grants MO1 RR00069, M01 RR00533, and M01 RR01271), and by the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (Contract N01-HD-3-3365).

Presented in part at the 13th Conference on Retroviruses and Opportunistic Infections, February 6, 2006, Denver, CO. Abstract number 710.

Correspondence to: Mark Mirochnick, MD, Boston Medical Center, Yawkey 2N-06, Boston, MA 02118 (e-mail: markm@bu.edu).

© 2008 Lippincott Williams & Wilkins, Inc.