Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
29
6
2021
Statut:
ppublish
Résumé
To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States. Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.36 - 0.54), whereas cobicistat AUC0--24 was 50% lower in the second trimester (n = 12, P = 0.0024, GMR = 0.50, 90% CI 0.36-0.69) and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.35-0.55). Placental transfer of darunavir and cobicistat was limited. Standard darunavir/cobicistat dosing during pregnancy results in significantly lower exposure during pregnancy, which may increase the risk of virologic failure and perinatal transmission.
Identifiants
pubmed: 34076612
doi: 10.1097/QAD.0000000000002857
pii: 00002030-202107010-00004
pmc: PMC8173003
mid: NIHMS1679717
doi:
Substances chimiques
Anti-HIV Agents
0
Cobicistat
LW2E03M5PG
Darunavir
YO603Y8113
Types de publication
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1191-1199Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068632
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069536
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106716
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission [30 September 2019]; Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf . [Accessed 20 October 2020]
Costantine MM. Physiologic and pharmacokinetic changes in pregnancy . Front Pharmacol 2014; 5:65.
Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy . Semin Perinatol 2015; 39:512–519.
Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women . Clin Pharmacokinet 2004; 43:1071–1087.
Stek A, Best BM, Wang J, Capparelli EV, Burchett SK, Kreitchmann R, et al. Pharmacokinetics of once versus twice daily darunavir in pregnant hiv-Infected Women . J Acquir Immune Defic Syndr 2015; 70:33–41.
Stek AM, Mirochnick M, Capparelli E, Best BM, Hu C, Burchett SK, et al. Reduced lopinavir exposure during pregnancy . AIDS 2006; 20:1931–1939.
Acosta EP, Bardeguez A, Zorrilla CD, Van Dyke R, Hughes MD, Huang S, et al. Pediatric AIDS Clinical Trials Group 386 Protocol Team. Pharmacokinetics of saquinavir plus low-dose ritonavir in human immunodeficiency virus-infected pregnant women . Antimicrob Agents Chemother 2004; 48:430–436.
Tracy TS, Venkataramanan R, Glover DD, Caritis SN. National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units. Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy . Am J Obstet Gynecol 2005; 192:633–639.
Papageorgiou I, Grepper S, Unadkat JD. Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines . Drug Metab Dispos 2013; 41:281–290.
Rakhmanina NY, van den Anker JN, Soldin SJ. Safety and pharmacokinetics of antiretroviral therapy during pregnancy . Ther Drug Monit 2004; 26:110–115.
Wang Y, Liu Z, Brunzelle JS, Kovari IA, Dewdney TG, Reiter SJ, Kovari LC, et al. The higher barrier of darunavir and tipranavir resistance for HIV-1 protease . Biochem Biophys Res Commun 2011; 412:737–742.
HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at: https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf . [Accessed 20 October 2020]
Crauwels HM, Osiyemi O, Zorrilla C, Bicer C, Brown K. Reduced exposure to darunavir and cobicistat in HIV-1-infected pregnant women receiving a darunavir/cobicistat-based regimen . HIV Med 2019; 20:337–343.
Tashima K, Crofoot G, Tomaka FL, Kakuda TN, Brochot A, Van de Casteele T, et al. Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial . AIDS Res Ther 2014; 11:39.
Curran A, Gutirerrez M, Deig E, Mateo G, Lopez RM, Imaz A, et al. Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients . J Antimicrob Chemother 2010; 65:2195–2203.
Boyd SD, Sampson MR, Viswanathan P, Struble KA, Arya V, Sherwat AI. Cobicistat-containing antiretroviral regimens are not recommended during pregnancy: viewpoint . AIDS 2019; 33:1089–1093.
Momper JD, Best BM, Wang J, Capparelli EV, Stek A, Barr E, et al. IMPAACT P1026s Protocol Team. Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV . AIDS 2018; 32:2507–2516.
Momper JD, Stek A, Wang J, Shapiro DE, Smith E, Chakhtoura N, et al . Pharmacokinetics of atazanavir boosted with cobicistat during pregnancy and postpartum . 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs . Noordwijk, Netherlands. 16 May 2019.
Molto J, Santos JR, Perez-Alvarez N, Cedeno S, Miranda C, Khoo S, et al. Darunavir inhibitory quotient predicts the 48-week virological response to darunavir-based salvage therapy in human immunodeficiency virus-infected protease inhibitor-experienced patients . Antimicrob Agents Chemother 2008; 52:3928–3932.
U.S. Food and Drug Administration. Office of Clinical Pharmacology Review Prezista® (NDA: 202895). Available at: https://www.fda.gov/files/drugs/published/202895--Darunavir-Clinpharm-BPCA.pdf . [Accessed 20 October 2020]
Mikula JM, Hsiao CB, Sawyer JR, Ma Q, Morse GD. Comparative effectiveness of darunavir 1,200 mg daily and approved dosing strategies for protease inhibitor-experienced patients . AIDS Res Treat 2013; 2013:687176.
Hakkola J, Raunio H, Purkunen R, Pelkonen O, Saarikoski S, Cresteil T, Pasanen M. Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy . Biochem Pharmacol 1996; 52:379–383.
Sarkar MA, Vadlamuri V, Ghosh S, Glover DD. Expression and cyclic variability of CYP3A4 and CYP3A7 isoforms in human endometrium and cervix during the menstrual cycle . Drug Metab Dispos 2003; 31:1–6.
Prezcobix (darunavir and cobicistat) [package insert].Titusville, New Jersey: Janssen Pharmaceutical Companies; 2015.
Honda M, Omori Y, Minei S, Oshiyama T, Shimizu M, Sanaka M, et al. Quantitative analysis of serum alpha 1-acid glycoprotein levels in normal and diabetic pregnancy . Diabetes Res Clin Pract 1990; 10:147–152.
Notarianni LJ. Plasma protein binding of drugs in pregnancy and in neonates . Clin Pharmacokinet 1990; 18:20–36.