Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/66721
Title: Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling
Authors: Stein Schalkwijk
Rob Ter Heine
Angela Colbers
Edmund Capparelli
Brookie M. Best
Tim R. Cressey
Rick Greupink
Frans G.M. Russel
José Moltó
Mark Mirochnick
Mats O. Karlsson
David M. Burger
Keywords: Medicine
Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-May-2019
Abstract: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. BACKGROUND: Darunavir 800 mg once (q24h) or 600 mg twice (q12h) daily combined with low-dose ritonavir is used to treat HIV-positive pregnant women. Decreased total darunavir exposure (17%-50%) has been reported during pregnancy, but limited data on unbound exposure are available. OBJECTIVES: To evaluate total and unbound darunavir exposures following standard darunavir/ritonavir dosing and to explore the value of potential optimized darunavir/ritonavir dosing regimens for HIV-positive pregnant women. PATIENTS AND METHODS: A population pharmacokinetic analysis was conducted based on data from 85 women. The final model was used to simulate total and unbound darunavir AUC0-τ and Ctrough during the third trimester of pregnancy, as well as to assess the probability of therapeutic exposure. RESULTS: Simulations predicted that total darunavir exposure (AUC0-τ) was 24% and 23% lower in pregnancy for standard q24h and q12h dosing, respectively. Unbound darunavir AUC0-τ was 5% and 8% lower compared with post-partum for standard q24h and q12h dosing, respectively. The probability of therapeutic exposure (unbound) during pregnancy was higher for standard q12h dosing (99%) than for q24h dosing (94%). CONCLUSIONS: The standard q12h regimen resulted in maximal and higher rates of therapeutic exposure compared with standard q24h dosing. Darunavir/ritonavir 600/100 mg q12h should therefore be the preferred regimen during pregnancy unless (adherence) issues dictate q24h dosing. The value of alternative dosing regimens seems limited.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072058593&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/66721
ISSN: 14602091
Appears in Collections:CMUL: Journal Articles

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