Send to

Choose Destination
Am J Kidney Dis. 2004 Jan;43(1):140-6.

Ribavirin pharmacokinetics in renal and liver transplant patients: evidence that it depends on renal function.

Author information

Department of Nephrology, Dialysis and Transplantation, CHU Rangueil, Toulouse, France.



Ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) infection. However, no recommendation exists for dosing patients with impaired renal function.


The authors performed a pharmacokinetic study in 21 HCV-positive renal or liver transplant patients. The mean creatinine clearance (ClCr) calculated by the Cockcroft-Gault equation was 57 mL/min (0.95 mL/s; range, 17 to 89 mL/min [0.28 to 1.48 mL/s]). Twelve blood samples were obtained during a 96-hour period after the first single administration of 1,000 mg of ribavirin. After the first pharmacokinetics (PK) and the pharmacodynamics (PD) profile was completed, the patients received ribavirin at 1,000 mg/d with or without interferon-alpha. A blood sample was taken monthly just before the oral administration of ribavirin. Plasma ribavirin concentrations were determined by high-performance liquid chromatography.


A total of 428 plasma concentrations were analyzed by a population pharmacokinetic method using the NONlinear Mixed Effect Model program. The mean observed ribavirin apparent clearance (CL/F) was 9.1 L/h (with an interindividual variability of 39%). The influences of the age, sex, body weight (BW), serum creatinine (Scr), ClCr, hemoglobin, and graft status on CL/F were examined. CL/F was highly correlated with ClCr (r = 0.63, P < 0.01). The final regression formula was CL/F (L/h) = 32.3 x BW x (1 - 0.0094 x age) x (1 - 0.42 x sex)/Scr, where sex = 0 for men and 1 for women; Scr is in micromoles per liter. Sex had a larger influence on CL/F than that corresponding to the Cockcroft-Gault equation (ie, 15%).


The authors present the parameters that determine ribavirin clearance in HCV+ transplant patients with normal or impaired renal function. Moreover, we suggest ribavirin daily doses according to various levels of renal function.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center