Pharmacokinetics of fosamprenavir plus ritonavir in human immunodeficiency virus type 1-infected adult subjects with hepatic impairment
| Autor: | Mary Beth Wire, José Hernández-Quero, Garrett Nichols, Yu Lou, Félix Gutiérrez, Franco Felizarta, Enrique Ortega, Bonaventura Clotet, María Larrousse Morellon, María J Pérez-Elías, Juan A. Pineda, Maribel Rodríguez-Torres |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Fosamprenavir HIV Infections Pharmacology Gastroenterology Antiviral Agents Amprenavir Young Adult Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) Dosing Furans Aged Sulfonamides Ritonavir biology business.industry Liver Diseases HIV Protease Inhibitors Middle Aged Organophosphates Regimen Infectious Diseases Enzyme inhibitor biology.protein HIV-1 Female Liver function Carbamates business medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 53(12) |
| ISSN: | 1098-6596 |
| Popis: | The effect of hepatic impairment on fosamprenavir/ritonavir pharmacokinetics was investigated. Sixty human immunodeficiency virus type 1-infected subjects, including 13, 20, and 10 subjects with mild, moderate, and severe hepatic impairment, respectively, and a comparator group of 17 subjects with normal hepatic function, were enrolled. Subjects with normal hepatic function received fosamprenavir at 700 mg plus ritonavir at 100 mg twice daily, whereas subjects with hepatic impairment received adjusted doses in anticipation of increased exposures. For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily delivered 17% higher values for the maximum plasma amprenavir concentration at the steady state ( C max ), 22% higher values for the area under the plasma concentration versus time curve over the dosing interval at the steady state [AUC (0- τ) ], similar values for the concentration at the end of the dosing interval ( C τ ), and 114% higher unbound C τ values. For subjects with moderate hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 27% lower plasma amprenavir C max values, 27% lower AUC (0-24) values, 57% lower C τ values, and 21% higher unbound amprenavir C τ values. For subjects with severe hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 19% lower plasma amprenavir C max values, 23% lower AUC (0-24) values, 38% lower C τ values, and similar unbound amprenavir C τ values. With a reduced ritonavir dosing frequency of 100 mg once daily, the plasma ritonavir AUC (0-24) values were 39% lower, similar, and 40% higher for subjects with mild, moderate, and severe hepatic impairment, respectively. The results of the study support the use of reduced fosamprenavir/ritonavir doses or dosing frequencies in the treatment of patients with hepatic impairment. No significant safety issues were identified; however, plasma amprenavir and ritonavir exposures were more variable in subjects with hepatic impairment, and those patients should be closely monitored for safety and virologic response. |
| Databáze: | OpenAIRE |
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