The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C
Article first published online: 3 APR 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 35, Issue 10, pages 1209–1220, May 2012
How to Cite
Brennan, B. J., Morcos, P. N., Wang, K., Blotner, S. D., Morrison, R., Hagedorn, C. H., Marbury, T. C., Sulkowski, M. and Grippo, J. F. (2012), The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C. Alimentary Pharmacology & Therapeutics, 35: 1209–1220. doi: 10.1111/j.1365-2036.2012.05079.x
- Issue published online: 15 APR 2012
- Article first published online: 3 APR 2012
- Manuscript Accepted: 7 MAR 2012
- Manuscript Revised: 16 FEB 2012
- Manuscript Revised: 23 JAN 2012
- Manuscript Received: 20 DEC 2011
Amongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) and ribavirin.
To evaluate the pharmacokinetics (PK) of PEG-IFN alfa-2a and ribavirin among these three groups.
Forty-seven patients with genotype 1 CHC (17 African Americans, 14 Hispanics and 16 Caucasians) received 8 weeks of PEG-IFN alfa-2a (180 &g/week) and ribavirin (1000 or 1200 mg/day). PEG-IFN alfa-2a serum concentrations and ribavirin plasma concentrations were measured following the first dose and at week 8. Pharmacokinetic parameters (Cmax, Tmax, AUC, CL/F) were estimated using noncompartmental methods.
There was no difference in the pharmacokinetic parameters for PEG-IFN alfa-2a following single-dose or steady-state administration between African American or Hispanic patients compared with Caucasian patients. Ribavirin pharmacokinetic parameters were similar between Hispanic and Caucasian patients for single-dose and steady-state administration. The single-dose Cmax was 33% lower (P < 0.05) in African American compared with Caucasian patients. Other ribavirin single-dose and steady-state pharmacokinetic parameters were slightly decreased (approximately 20% lower) in African American patients, but were not considered clinically meaningful.
No differences were observed in PEG-IFN alfa-2a pharmacokinetic parameters between African American or Hispanic patients compared with Caucasian patients. For ribavirin, no differences were observed in pharmacokinetic parameters between Hispanic and Caucasian patients. While a trend towards increased ribavirin clearance and decreased exposure was observed in African American patients vs. Caucasian patients, the differences were small and not considered clinically meaningful (Clinical Trial Number: NP17354).