PHARMACOKINETICS OF RIBAVIRIN AND URINARY-EXCRETION OF THE MAJOR METABOLITE 1,2,4-TRIAZOLE-3-CARBOXAMIDE IN NORMAL VOLUNTEERS

Ribavirin (1-B-D-ribofuranosyl-1,2,4-trtazole-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 (7,2,4-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 l/h. 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 4.1% after oral administration).