Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling.
J Antimicrob Chemother
; 74(5): 1348-1356, 2019 05 01.
Article
in En
| MEDLINE
| ID: mdl-30715324
ABSTRACT
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 ANDMETHODS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Complications, Infectious
/
HIV Seropositivity
/
Ritonavir
/
Anti-HIV Agents
/
Darunavir
/
Models, Theoretical
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
J Antimicrob Chemother
Year:
2019
Type:
Article
Affiliation country:
Netherlands