Pharmacokinetics of ribavirin in patients with hepatitis C virus.
OBJECTIVE
A population pharmacokinetic analysis was performed using plasma concentration data (n = 7025) from 380 patients to examine the relationship between ribavirin dose and its pharmacokinetics.


METHODS
Ribavirin pharmacokinetics were described by a three-compartment model with sequential zero-order and a first-order absorption processes. Interoccasion variability and food effects were included.


RESULTS
Lean body weight (range 41-91 kg) was the only covariate with a clinically significant influence on ribavirin pharmacokinetics, affecting clearance (15.3-23.9 l h(-1)) and the volume of the larger peripheral compartment.


CONCLUSIONS
The model provided a good description of the available data, confirmed by accurate estimates of parameter values and low residual variability (17%).
Wade
Janet R
JR
Exprimo NV, Lummen, Belgium.
Snoeck
Eric
E
Duff
Frank
F
Lamb
Matthew
M
Jorga
Karin
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D004338:Drug Combinations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a