title: Plasma and intracellular ribavirin concentrations are not significantly altered by abacavir in hepatitis C virus-infected patients.
abstract: The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations.
  
  
  
  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 were measured 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.
  
  
  
  Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded for missed 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 different with 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/10(6) 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 events were 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.
  
  
  
  Abacavir did not significantly alter ribavirin or ribavirin triphosphate concentrations.
authors: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Edward J
authors: EJ
authors: Fuchs
authors: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA.
authors: Jennifer J
authors: JJ
authors: Kiser
authors: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Craig W
authors: CW
authors: Hendrix
authors: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Mark
authors: M
authors: Sulkowski
authors: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Christine
authors: C
authors: Radebaugh
authors: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA.
authors: Lane
authors: L
authors: Bushman
authors: Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA.
authors: Michelle L
authors: ML
authors: Ray
authors: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA aandrade@jhmi.edu.
authors: Adriana
authors: A
authors: Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D003600:Cytosol / Q000737:chemistry*; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult; D000099227:Abacavir
chemical_list: D000998:Antiviral Agents; D015224:Dideoxynucleosides; D012254:Ribavirin; D000099227:Abacavir