The clinical pharmacology of ribavirin

Abstract

This article summarizes pharmacokinetic studies of ribavirin in healthy volunteer and patient populations. Ribavirin is rapidly absorbed after oral administration (time to maximum concentration = 1.5 hours), followed by rapid distribution and prolonged elimination phases. Uptake from the proximal small bowel is active via concentrative N1 sodium-dependent nucleoside transporters. Ribavirin appears to be extensively absorbed; however, absolute bioavailability is approximately 50%, probably due to first-pass metabolism. Apparent volume of distribution is extensive (approximately 2,000 L) due to ribavirin's distribution into nonplasma (cellular) compartments, which occurs via es-nucleoside transporters. Ribavirin does not bind to plasma proteins. Upon multiple dosing there is extensive accumulation in plasma, and steady state is achieved by approximately 4 weeks. Because of slow elimination of ribavirin from nonplasma compartments, the multiple dose half-life is approximately 298 hours. The pharmacokinetic properties of ribavirin in special populations, the effect of food on ribavirin's pharmacokinetics, and the potential interactions between ribavirin and other agents are also reviewed.