TY - JOUR
T1 - Rilpivirine pharmacokinetics without and with darunavir/ritonavir once daily in adolescents and young adults
AU - Foca, Marc
AU - Yogev, Ram
AU - Wiznia, Andrew
AU - Hazra, Rohan
AU - Jean-Philippe, Patrick
AU - Graham, Bobbie
AU - Britto, Paula
AU - Carey, Vincent J.
AU - King, Jennifer
AU - Acosta, Edward P.
AU - Cressey, Tim R.
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Background: 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. Methods: 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. Results: 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 AUC 0-24, C max and C 24 h were 2.38 μg h/mL (1.92-2.94), 0.14 μg/mL (0.12-0.18) and 0.07 μg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC 24, C max and C 24 h were 6.74 μg h/mL (4.89-9.28), 0.39 μg/mL (0.27-0.57) and 0.23 μg/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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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 AUC 0-24, C max and C 24 h were 2.38 μg h/mL (1.92-2.94), 0.14 μg/mL (0.12-0.18) and 0.07 μg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC 24, C max and C 24 h were 6.74 μg h/mL (4.89-9.28), 0.39 μg/mL (0.27-0.57) and 0.23 μg/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. Conclusions: 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.
KW - adolescents
KW - antiretrovirals
KW - darunavir
KW - pediatrics
KW - rilpivirine
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UR - http://www.scopus.com/inward/citedby.url?scp=84969217101&partnerID=8YFLogxK
U2 - 10.1097/INF.0000000000001214
DO - 10.1097/INF.0000000000001214
M3 - Article
C2 - 27187753
AN - SCOPUS:84969217101
SN - 0891-3668
VL - 35
SP - e271-e274
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 9
ER -