The ARRIBA Concept: Adequate Resorption of Ribavirin

Abstract

Background

Adequate ribavirin exposure is essential for optimal sustained virological response (SVR) rates in chronic HCV treatment. It has been proposed that the area under the concentration-time curve up to 4 h after intake of ribavirin (AUC_{0–4 h}) of the first weight-based ribavirin dose should be ≥1.755 mg•h/l to guarantee the highest chance of SVR. Our ARRIBA concept comprises a test dose of ribavirin to select the optimal starting dose to achieve adequate exposure. This study aims to evaluate whether adequate exposure can be achieved after dose advice based on the AUC_{0–4 h} of a single weight-based ribavirin test dose.

Methods

(Formerly) HCV-infected subjects received a single weight-based ribavirin test dose (<75 kg: 400 mg; ≥75 kg: 600 mg) and the AUC_{0–4 h} was calculated. If ribavirin AUC_{0–4 h} was ≥1.755 mg•h/l, subjects received the same dose 4 weeks later; if the AUC_{0–4 h} was <1.755 mg•h/l, an adjusted dose was administered. The ribavirin AUC_{0–4 h} was recorded again. The primary outcome was the proportion of subjects with an AUC_{0–4 h} ≥1.755 mg•h/l after the second dose.

Results

A total of 26 subjects were included. The geometric mean (95% CI) ribavirin AUC_{0–4 h} was 1.67 (1.44–1.92) mg•h/l with 9 subjects (35%) reaching the target AUC on day 1. Thus, on day 29, 17 subjects (65%) received an adjusted dose. The geometric mean (95% CI) AUC_{0–4 h} increased to 1.90 (1.62–2.21) mg•h/l and then 16 subjects (62%) had an AUC_{0–4 h} ≥1.755 mg•h/l, which is significantly higher than day 1 (P<0.05).

Conclusions

Our ARRIBA concept of a ribavirin test dose, with dose adjustment if necessary, leads to an increased proportion of patients with an AUC≥1.755 mg•h/l compared to traditional weight-based ribavirin dosing.