Pharmacokinetics of ribavirin and urinary excretion of the major metabolite 1,2,4-triazole-3-carboxamide in normal volunteers.
Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad spectrum antiviral agent, with a primary indication in human immunodeficiency virus (HIV) infection, but with significant activity against more common viral pathogens. Since the available kinetic data are only in HIV patients, a study was carried out in normal volunteers, also with the objective of obtaining data on the biotransformation of the drug. A specific HPLC method was used to determine both the unchanged drug and its major metabolite (1,2,4-triazole-3-carboxamide). The unchanged drug was confirmed to have a long plasma half-life, ranging from 30.4 to 61.0 h with a total clearance of 20.3 +/- 10.6 1 h-1. The comparison of oral and i.v. administrations, showed 32.6 +/- 16.7% oral bioavailability. By investigating the urinary excretion of the unchanged drug and its metabolite, it was shown that the percentage of the metabolite is almost doubled after oral administration (28.8% vs 6.2% after i.v.) with a corresponding inverse difference in the percentages of urinary unchanged ribavirin (16.7% after i.v. vs 4.4% after oral administration).
Paroni
R
R
Istituto Scientifico H. S. Raffaele, Milan, Italy.
Del Puppo
M
M
Borghi
C
C
Sirtori
C R
CR
Galli Kienle
M
M
D000328:Adult; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012263:Ribonucleosides / Q000493:pharmacokinetics*; D014230:Triazoles / Q000493:pharmacokinetics* / Q000652:urine
D012263:Ribonucleosides; D014230:Triazoles; C017957:1,2,4-triazole-3-carboxamide; D012254:Ribavirin