An In Vitro Study of the Uptake and Release of Ribavirin and It's Effect on the Osmotic Fragility of Rat, Rhesus Monkey and Human Erythrocytes

Abstract

Recent studies indicate that ribavirin, a synthetic antiviral agent, may have an unusual affinity for rhesus monkey erythrocytes not detected in rat erythrocytes (14). Experiments were designed to estimate the uptake and release of ribavirin at 4°C and 37°C, via ¹⁴C-ribavirin, and to determine the drug's effect on osmotic fragility of rat, rhesus monkey and human erythrocytes. The results of the uptake studies show that monkey RBC's have a much stronger affinity for ribavirin than either rat or human RBC's and that uptake of ribavirin at 37°C is an energy requiring process. The release of ribavirin is an apparent equilibrium reaction that proceeds, via facilitated diffusion, in the direction of the concentration gradient: Free Rib⇆ Rib-P ⇆ Rib-P-P ⇆ Rib-P-P-P The osmotic fragility curves of fresh RBC's from the respective species, incubated 2.5 hours with ribavirin, showed no significant change from the control curves. However, monkey RBC's incubated 2.5 hours with 4095 μM ribavirin and an additional 21.5 hours in drug-free media became significantly more resistant to osmotic lysis. Rat and human RBC's similarly treated were not detectably affected. These data indicate that the uptake and release mechanisms for ribavirin are similar for all three species and that the effect of ribavirin on the osmotic fragility of fresh RBC's is not detectable.