Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults
| Autor: | Rohan Hazra, Vincent J. Carey, Tim R. Cressey, Bobbie Graham, Andrew Wiznia, Amy Gonzalez, Paula Britto, Ram Yogev, Kajal B. Larson, Patrick Jean-Philippe, Edward P. Acosta |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent Anti-HIV Agents 030106 microbiology Etravirine HIV Infections Gastroenterology 03 medical and health sciences Young Adult Pharmacokinetics Internal medicine Nitriles Medicine Humans Child Darunavir Sulfonamides Ritonavir business.industry Area under the curve General Medicine Confidence interval Pyridazines Regimen Infectious Diseases Pyrimidines Pediatrics Perinatology and Child Health Female business Original Articles and Commentaries medicine.drug Blood sampling |
| Zdroj: | Journal of the Pediatric Infectious Diseases Society. 5(2) |
| ISSN: | 2048-7207 |
| Popis: | BACKGROUND Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults. METHODS Human immunodeficiency virus-infected subjects 9 to < 24 years old on optimized background therapy including DRV/r 800/100 mg QD alone or combined with ETR 200 mg BID or ETR 400 mg QD were enrolled. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. Intensive 24-hour blood sampling was performed, and PK parameters were determined using noncompartmental analysis. RESULTS Thirty-one subjects (14 males) completed the study; 16 received DRV/r QD alone (group 1), 6 received DRV/r plus ETR BID (group 2A), and 9 received DRV/r plus ETR QD (group 2B). The geometric mean (90% confidence interval [CI] geometric mean) for DRV area under the curve at 24 hours (AUC24) was 57.9 (49.6-67.6), 74.9 (44.4-126.5), and 66.4 (50.8-86.9) mg × h/L for patients in groups 1, 2A, and 2B, respectively. The increased DRV exposure when coadministered with ETR was not statistically significant. The geometric mean (90% CI geometric mean) of ETR AUC24 was 8.6 (4.4-16.8) and 11.9 (7.5-18.9) mg × h/L for groups 2A and 2B, respectively, with comparable C24. CONCLUSIONS The results suggest that DRV/r QD with ETR 400 mg QD or 200 mg BID is appropriate and support further evaluation of the safety and efficacy of the once-daily regimen in older children, adolescents, and young adults. |
| Databáze: | OpenAIRE |
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