Ribavirin Levels 50% Higher With Than Without Telaprevir

14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013, Amsterdam

Mark Mascolini

Ribavirin area under the concentration-time curve (AUC) was 50% higher with telaprevir than without telaprevir in 21 HCV-positive people enrolled in a trial of telaprevir plus pegylated interferon/ribavirin (PR) versus PR alone [1]. That finding, and other study results, could partly explain why anemia is more frequent with than without telaprevir in people taking PR.

Both telaprevir and boceprevir, the other licensed HCV protease inhibitor, contribute to anemia in people taking PR for HCV. Pinning down the mechanism is difficult because telaprevir, boceprevir, and ribavirin all may contribute independently to anemia risk.

This analysis included 21 treatment-naive people infected with HCV genotype 1 and enrolled in an ongoing trial of telaprevir plus PR versus PR alone (NCT01097395). Five people were taking triple therapy and 16 only PR. Ribavirin dose was based on weight, either 1000 or 1200 mg. After 9 to 14 weeks of therapy--with ribavirin levels at steady state--the researchers collected plasma, red blood cells, and peripheral blood mononuclear cell (PBMC) samples before and up to 12 hours after dosing.

Median ages were 56 and 50 in the triple-therapy and dual-therapy groups, while median respective weights were 78 and 77. All triple-therapy patients were men, as were 9 of 15 dual-therapy patients. Three people (60%) in the triple-therapy group and 5 (32%) in the dual-therapy group had fibrosis stage 3-4.

Ribavirin AUC was 1.54 times higher in the triple-therapy group than in people not taking telaprevir (P = 0.002). In red blood cells, ribavirin monophosphate, diphosphate, and triphosphate were 3.3-fold (P = 0.03), 2.3-fold (P = 0.0005), and 2.4-fold (P = 0.001) higher with than without telaprevir. In PBMCs, ribavirin mono-, di-, and triphosphate levels were 2.5-fold (P = 0.003), 3-fold (P = 0.006), and 2-fold (P = 0.04) higher with than without telaprevir.

The researchers "speculate that increased ribavirin exposures due to telaprevir might be a factor in the anemia observed during telaprevir-based antiviral therapy of HCV."

Reference

1. Hammond KP, Jimmerson L, MacBrayne CE, et al. Increased plasma and intracellular ribavirin concentrations associated with telaprevir use. 14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013,

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