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Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling
Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands;Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, RIMLS, Med Ctr, Nijmegen, Netherlands.
Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
Radboud Univ Nijmegen, RIHS, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA;Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 5, p. 1348-1356Article in journal (Refereed) Published
Abstract [en]

Background: Darunavir 800mg 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 AUC(0-tau) and C-trough during the third trimester of pregnancy, as well as to assess the probability of therapeutic exposure. Results: Simulations predicted that total darunavir exposure (AUC(0-tau)) was 24% and 23% lower in pregnancy for standard q24h and q12h dosing, respectively. Unbound darunavir AUC(0-tau) 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.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2019. Vol. 74, no 5, p. 1348-1356
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Infectious Medicine
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URN: urn:nbn:se:uu:diva-393535DOI: 10.1093/jac/dky567ISI: 000482043300029PubMedID: 30715324OAI: oai:DiVA.org:uu-393535DiVA, id: diva2:1354034
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved

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Karlsson, Mats

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