Pharmacokinetics and safety of single-dose ribavirin in patients with chronic renal impairment

Drug Discov Ther. 2013 Aug;7(4):158-63.

Abstract

This open-label study assessed the pharmacokinetics of a single 400-mg oral dose of ribavirin in 6 healthy volunteers and 18 subjects with varying degrees of renal impairment (mild:creatinine clearance [CLcr] 61-90 mL/min/1.73 m², moderate: CLcr 31-60 mL/min/1.73 m(2), severe: CLcr 10-30 mL/min/1.73 m², n = 6 in each group). Blood and urine samples were collected pre-dose and up to 168 hours post-dose for pharmacokinetic analyses. Compared with control subjects, ribavirin area under the plasma concentration-time curve from time zero to the time of the final quantifiable sample (AUC(tf)) and maximum plasma concentration (C(max)) values were increased, and apparent clearance (CL/F), clearance (CLr), and amount excreted (Ae) values were reduced in subjects with renal impairment. Mean ribavirin AUC(tf) was increased 2- to 3-fold in patients with moderate-severe renal impairment compared with control subjects. Ribavirin CL/F and CLr were significantly correlated with CLcr. Single-dose ribavirin was safe and well tolerated in all subjects. The pharmacokinetics of ribavirin were substantially altered in subjects with stable chronic renal impairment, possibly reflecting changes in ribavirin metabolism associated with renal impairment.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Area Under Curve
  • Biomarkers / blood
  • Creatinine / blood
  • Female
  • Humans
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Linear Models
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Models, Biological
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / physiopathology
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects
  • Ribavirin / blood
  • Ribavirin / pharmacokinetics*
  • Severity of Illness Index
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • Ribavirin
  • Creatinine