Plasma and intracellular ribavirin concentrations are not significantly altered by abacavir in hepatitis C virus-infected patients

Abstract

Objectives: The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations. Methods: Hepatitis C virus-infected subjects who had been cured or failed prior treatment were randomized to 8 weeks of ribavirin alone (N=14; weight-based dosing) or weight-based ribavirin+abacavir (N=14; 300 mg orally every 12 h). Ribavirin trough concentrations weremeasured on days 14, 28, 42 and 56; PBMCs for ribavirin triphosphate determination were sampled on days 28 and 56, pre-dose and at 6 and 12 h post-dose. ClinicalTrials.gov: NCT01052701. Results: Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded formissed pharmacokinetic visits. Fourteen subjects received ribavirin+abacavir and 12 received ribavirin alone. Mean±SD plasma ribavirin trough concentrations (μg/mL) on days 14, 28, 42 and 56, respectively, were not significantly differentwith coadministration of abacavir (1.54±0.60, 1.93±0.54, 2.14±0.73 and 2.54±1.05) compared with ribavirin alone (1.48±0.32, 2.08±0.41, 2.32±0.47 and 2.60±0.62) (P>0.40). Mean ribavirin triphosphate intracellular concentrations (pmol/106 cells) on days 28 and 56, respectively, did not differ statistically between abacavir users (11.98±9.86 and 15.87±12.52) and non-users (15.91±15.58 and 15.93±12.69) (P>0.4). Adverse eventswere mild or moderate, except for three grade 3 occurrences of transaminitis, cholecystitis and low absolute neutrophil count that resolved and were judged not attributable to study medications. Conclusions: Abacavir did not significantly alter ribavirin or ribavirin triphosphate concentrations.