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dc.contributor.authorJin, Runyan
dc.contributor.authorCai, Ling
dc.contributor.authorMcHutchison, J. G.
dc.contributor.authorDowling, Thomas C.
dc.contributor.authorHowell, Charles D.
dc.date.accessioned2013-02-28T16:54:42Z
dc.date.available2013-02-28T16:54:42Z
dc.date.issued2012-11
dc.identifier.citationJin, R., Cai, L., McHutchison, J. G., Dowling, T. C., & Howell, C. D. (2012). Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1. American Journal of Gastroenterology, 107(11), 1675-1683, DOI: 10.1038/ajg.2012.306.en_US
dc.identifier.urihttp://hdl.handle.net/10713/2339
dc.descriptionSUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg. Author affiliations: School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA, Duke Clinical Research Institute & Division of Gastroenterology, Duke University , Durham , North Carolina , USA ; 4 Department of Medicine, University of Maryland School of Medicine , Baltimore , Maryland , USA.en_US
dc.description.abstractOBJECTIVES: Peginterferon and ribavirin treatment is less effective for hepatitis C virus (HCV) genotype 1 infections in African Americans (AA) compared with Caucasian Americans (CA). Host genetic variability near the interleukin-28B (IL28B) gene locus is partly responsible. We investigated the relationship between ribavirin drug exposure and week 24 and 72 (sustained virologic response, SVR) responses (undetected serum HCV RNA) in 71 AA and 74 CA with HCV genotype 1 who received >90% of the prescribed peginterferon and weight-based ribavirin (1,000 or 1,200 mg per day) from week 1 to 24. METHODS: Ribavirin plasma levels were measured at weeks 1, 2, 4, 8, 12 and 24; ribavirin area under the concentration vs. time curve (AUC) was calculated using the linear trapezoidal rule. RESULTS: Compared with CA, AA had lower week 24 (WK24VR) (57.8 vs. 78.1; P<0.05) and week 72 (SVR) (36.6% vs 54.8%; P<0.05) response rates. AA also had significantly lower ribavirin exposure (AUC) from week 1 to 12 (P<0.05). Ribavirin exposures ≥4,065 and ≥4,480 ng/ml/day in the first week (AUC(0-7)) were thresholds for WK24VR and SVR in receiver-operating characteristic curve analyses. AA were less likely to have a threshold ribavirin AUC(0-7) level than CA (P<0.05). There were no significant racial differences in WK24VR (AA: 77 vs. CA: 84%) and SVR (AA: 52 vs. CA: 60%) rates in patients who met the ribavirin AUC(0-7) thresholds. Ribavirin AUC(0-7) predicted WK24VR and SVR independently of IL28B single-nucleotide polymorphism rs12979860 genotype. Yet, achieving threshold AUC(0-7) levels increased response rates primarily in AA with the less favorable non-C/C genotypes. CONCLUSIONS: Standard weight-based dosing leads to suboptimal ribavirin exposure in AA and contributes to the racial disparity in peginterferon and ribavirin treatment efficacy for HCV genotype 1.en_US
dc.language.isoen_USen_US
dc.subject.meshAfrican Americans--geneticsen_US
dc.subject.meshAntiviral Agents--administration & dosageen_US
dc.subject.meshAntiviral Agents--therapeutic useen_US
dc.subject.meshChi-Square Distributionen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHepatitis C, Chronic--drug therapyen_US
dc.subject.meshHepatitis C, Chronic--geneticsen_US
dc.subject.meshInterferon-alpha--administration & dosageen_US
dc.subject.meshLogistic Modelsen_US
dc.subject.meshPolyethylene Glycols--administration & dosageen_US
dc.subject.meshRecombinant Proteins--administration & dosageen_US
dc.subject.meshRibavirin--administration & dosageen_US
dc.titleOptimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1en_US
dc.typeArticleen_US
dc.description.versionYesen_US
dc.identifier.doi10.1038/ajg.2012.306
dc.identifier.pmid23090351
dc.identifier.ispublishedYesen_US
dc.description.urinameFull Texten_US
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