Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling
| Autor: | Schalkwijk, Stein, Ter Heine, Rob, Colbers, Angela, Capparelli, Edmund, Best, Brookie M, Cressey, Tim R, Greupink, Rick, Russel, Frans GM, Moltó, José, Mirochnick, Mark, Karlsson, Mats O, Burger, David M |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Ritonavir
Anti-HIV Agents Population Infectious Gestational Age Reproductive health and childbirth Pharmacology and Pharmaceutical Sciences Microbiology Pregnancy Complications Dose-Response Relationship Theoretical Pregnancy Models Medical Microbiology 6.1 Pharmaceuticals HIV Seropositivity Humans HIV/AIDS Computer Simulation Female Drug Infection Darunavir |
| Zdroj: | Journal of Antimicrobial Chemotherapy r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname The Journal of antimicrobial chemotherapy, vol 74, iss 5 |
| ISSN: | 0305-7453 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|