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Antimicrobial Agents and Chemotherapy, February 2004, p. 430-436, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.430-436.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Saquinavir plus Low-Dose Ritonavir in Human Immunodeficiency Virus-Infected Pregnant Women

University of Alabama at Birmingham, Birmingham, Alabama,¹ University of Medicine and Dentistry of New Jersey, Newark, New Jersey,² University of Puerto Rico,³ San Juan City Hospital, San Juan, Puerto Rico,¹⁰ Tulane University Medical School, New Orleans, Louisiana,⁴ Harvard School of Public Health, Boston, Massachusetts,⁵ University of Southern California, Los Angeles, California,⁶ Columbia University College, New York, New York,⁷ National Institute of Child Health and Human Development, Rockville,⁸ Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland⁹

Received 3 July 2003/ Returned for modification 18 September 2003/ Accepted 14 October 2003

The physiologic changes that occur during pregnancy make it difficult to predict antiretroviral pharmacokinetics (PKs), but few data exist on the PKs of protease inhibitors in human immunodeficiency virus (HIV)-infected pregnant women. The objective of the present study was to determine the PKs of ritonavir (RTV)-enhanced saquinavir (SQV) in HIV-infected pregnant women by an area under the curve (AUC)-targeted approach. A phase I, formal PK evaluation was conducted with HIV-infected pregnant woman during gestation, during labor and delivery, and at 6 weeks postpartum. The SQV-RTV regimen was 800/100 mg twice a day (b.i.d.), and nucleoside analogs were administered concomitantly. The SQV exposure targeted was an AUC at 24 h of 10,000 ng · h/ml. Participants were evaluated for 12-h steady-state PKs at each time period. Thirteen subjects completed the PK evaluations during gestation, 7 completed the PK evaluations at labor and delivery, and 12 completed the PK evaluations postpartum. The mean baseline weight was 67.4 kg, and the median length of gestation was 23.3 weeks. All subjects achieved SQV exposures in excess of the target AUC. The SQV AUCs at 12 h (AUC₁₂s) during gestation (29,373 ± 17,524 ng · h/ml [mean ± standard deviation]), during labor and delivery (26,189 ± 22,138 ng · h/ml), and during the postpartum period (35,376 ± 26,379 ng · h/ml) were not significantly different. The mean values of the PK parameters for RTV were lower during gestation than during the postpartum period: for AUC₁₂, 7,811 and 13,127 ng · h/ml, respectively; for trough concentrations, 376 and 632 ng/ml, respectively; and for maximum concentrations, 1,256 and 2,252 ng/ml, respectively (P 0.05 for all comparisons). This is the first formal PK evaluation of a dual protease inhibitor regimen with HIV-infected pregnant women. The level of SQV exposure was sufficient at each time of evaluation. These data demonstrate large variability in SQV and RTV concentrations and suggest that RTV concentrations are altered by pregnancy. These PK results suggest that SQV-RTV at 800/100 mg b.i.d. appears to be a reasonable treatment option for this population.

This report is dedicated in the memory of Jane Pitt, whose clinical and scientific contributions to this field will always be remembered.

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