Brief Report: Dolutegravir Plasma Protein Binding and Unbound Concentrations During Pregnancy and Postpartum.

Autor:	Momper JD; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA., Nikanjam M; School of Medicine, University of California, San Diego, La Jolla, CA., Best BM; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA.; School of Medicine, University of California, San Diego, La Jolla, CA., Mirochnick M; Department of Pediatrics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA., Capparelli EV; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA.; School of Medicine, University of California, San Diego, La Jolla, CA., Cressey TR; AMS-PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; and.; Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2023 Dec 01; Vol. 94 (4), pp. 332-336.
DOI:	10.1097/QAI.0000000000003281
Abstrakt:	Background: Clinical interpretation of the reduced dolutegravir (DTG) plasma concentrations reported during pregnancy is complicated by its high plasma protein binding. Plasma proteins significantly decrease during pregnancy, and understanding changes in DTG protein binding and its therapeutically active unbound concentrations are necessary to evaluate the impact of pregnancy changes on DTG pharmacokinetics. Methods: Retrospective assessment of plasma samples from pregnant women living with HIV enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s study receiving 50 mg DTG film-coated tablets once daily as part of clinical care. Unbound and total DTG concentrations were determined predose (C0) and at maximum (Cmax) concentrations during the second trimester (2T), third trimester (3T), and postpartum (PP). Percentage unbound was calculated as the ratio of ultrafiltrate unbound DTG concentration to total DTG concentration. Results: Twenty-nine mothers were included for protein binding evaluations; 15, 27, and 23 from the 2T, 3T, and PP, respectively. DTG % unbound for C0 and Cmax were significantly different by stage of pregnancy, with 3T significantly higher compared with PP; 1.02% vs. 0.69% (P = 0.0067) for C0 and 0.76% vs. 0.46% for Cmax (P = 0.0056). Median (IQR) unbound concentrations for C0 were 6.3 (4.7-18.4) for the 2T, 8.0 (5.6-16.9) for the 3T, and 13.3 (8.4-22.7) ng/mL PP, significantly different between 2T and PP (P = 0.0039), but not different between 3T and PP (P = 0.46). Conclusion: Lower total DTG plasma concentrations during pregnancy coincide with temporal decreases in DTG protein binding, resulting in comparable unbound DTG concentrations during the 3T and PP. Competing Interests: The authors have no funding or conflicts of interest to disclose. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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