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Rilpivirine Pharmacokinetics Without and With Darunavir/Ritonavir Once Daily in Adolescents and Young Adults.


ABSTRACT: Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions between RPV and DRV/r once daily in adolescents and young adults.Human immunodeficiency virus-infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25?mg once daily without or combined with DRV/r 800/100?mg once daily were enrolled. Intensive 24-hour blood sampling was performed, and PK indices were determined using noncompartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen.Fifteen subjects receiving RPV without and 14 subjects with DRV/r were enrolled. When dosed without DRV/r, the RPV geometric mean (90% confidence interval) for RPV AUC0-24, Cmax and C24 h were 2.38 ?g h/mL (1.92-2.94), 0.14 ?g/mL (0.12-0.18) and 0.07 ?g/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24 h were 6.74 ?g h/mL (4.89-9.28), 0.39 ?g/mL (0.27-0.57) and 0.23 ?g/mL (0.17-0.32), respectively, well above the target ranges based on adult data. DRV/r PK was not affected by coadministration of RPV.RPV PK in this adolescent population was similar to adults when dosed without DRV/r. DRV/r coadministration increased RPV exposure 2- to 3-fold, indicating that drug-related side effects should be closely monitored.

SUBMITTER: Foca M 

PROVIDER: S-EPMC5245132 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Rilpivirine Pharmacokinetics Without and With Darunavir/Ritonavir Once Daily in Adolescents and Young Adults.

Foca Marc M   Yogev Ram R   Wiznia Andrew A   Hazra Rohan R   Jean-Philippe Patrick P   Graham Bobbie B   Britto Paula P   Carey Vincent J VJ   King Jennifer J   Acosta Edward P EP   Cressey Tim R TR  

The Pediatric infectious disease journal 20160901 9


<h4>Background</h4>Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions betwe  ...[more]

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