The end-of-treatment ribavirin concentration predicts HCV relapse

 Ther Drug Monit. 2013 Aug 12. [Epub ahead of print]

The end-of-treatment ribavirin concentration predicts HCV relapse

Bodeau S, Durand-Maugard C, Lemaire-Hurtel AS, François C, Castelain S, Helle F, Andréjak M, Nguyen-Khac E, Duverlie G, Brochot E.

 

Source

*Departments of Pharmacology and †Virology, Amiens University Medical Center; ‡Virology Research Unit, EA 4294, Jules Verne University of Picardie; and §Department of Hepatogastroenterology, Amiens University Medical Center, Amiens, France.

Backgrounds and aims: The optimization of combination therapy with ribavirin (RBV) and pegylated interferon alpha has substantially improved sustained virologic response (SVR) rates and lowered virologic relapse rates in patients infected with hepatitis C virus (HCV). In order to improve therapeutic of patients infected with HCV in our hospital, we developed a LC/ESI-MS-MS ribavirin assay. We then conducted a retrospective study of the relationship between the end-of-treatment plasma RBV concentration and virologic relapse.

Methods: Thirty-four HCV patients treated with PEG-IFN/RBV and with an end-of-treatment response were assayed for plasma ribavirin concentration on the last day of treatment by LC/ESI-MS-MS with a triple quadrupole mass spectrometer (3200 QTRAP, ABsciex, Les Ulis, France) in positive-ion selected reaction monitoring mode. [13C5]-Ribavirin has been used as internal standard. CV of intra-day repeatability of the technique varies from 2.53 to 8.49 % and inter-day repeatability from 2.98 to 10.74 %. The technique is linear from 7.5 to 10 000 ng/mL and the lower limit of detection is 4.5 ng/mL.

Results: Eleven patients (32.4%) relapsed and 23 patients (67.6%) achieved an SVR.

 

The mean plasma ribavirin concentration on the last day of treatment was 1380 ng/mL for relapse patients and 2278 ng/mL for SVR patients (p=1.44x10-6).

 

A receiver operating characteristic analysis showed that a threshold of 1960 ng/mL was associated with the greatest sensitivity and specificity (100% and 83% respectively, with an area under the curve of 0.94; p<0.0001) for discriminating between relapse patients and non-relapse patients. A bivariate analysis indicated that a plasma ribavirin concentration

Discussion and conclusion: Our study results highlight the relevance of measuring plasma ribavirin concentrations during and at the end of treatment, with a view to avoiding virologic relapse. These findings should be analyzed in the context of three-drug combination therapy (with a revaluation of the relevance of the therapeutic drug monitoring of ribavirin) in order to optimize the sustained virologic response (SVR) rate.

Keywords : Therapeutic drug monitoring, ribavirin, Hepatitis C virus, LC-MS/MS

PMID:23942546 [PubMed - as supplied by publisher]