The current study was carried out to evaluate pharmacokinetic profiles of
viramidine and
ribavirin in patients (n = 8 per dose group) with compensated
hepatitis C infection following oral dosing of
viramidine (400, 600, or 800 mg bid for 4 weeks). Pharmacokinetic parameters were determined on days 1 and 29 based on plasma, red blood cell, and urine concentrations of
viramidine and
ribavirin. The results indicate rapid absorption and conversion of
viramidine to
ribavirin after
oral administration of
viramidine.
Viramidine and
ribavirin exposure in plasma and RBCs generally increased from the 400- to 600-mg dose level of
viramidine. However, no further increase in exposure was noted at the 800-mg dose. Long half-lives for
viramidine (66-76 hours in plasma and 200-420 hours in red blood cells) and
ribavirin (340-410 hours in plasma and 360-430 hours in red blood cells) were noted. A negligible amount of
viramidine (1%-4% of dose) and a small amount of
ribavirin (9%-14% of dose) were excreted in the urine. The renal clearance was low for both
viramidine (5-8 L/h) and
ribavirin (4-7 L/h). Significant accumulation of
viramidine was noted in red blood cells (accumulation factor [R] = 5-8) but not in plasma (R = 2). Extensive accumulation of
ribavirin was noted in both plasma (R = 9-17) and red blood cells (R = 77-129). Steady-state levels of
ribavirin and
viramidine in plasma and red blood cells were achieved by day 22. At steady state, there was extensive conversion of
viramidine to
ribavirin in both plasma and red blood cells. Both
viramidine and
ribavirin were preferentially distributed into red blood cells than plasma.