Preclinical evaluation in monkeys of a ribavirin regimen proposed for use in Lassa fever patients

Abstract The nucleoside, ribavirin (1-β- d -ribofuranosyl-1,2,4-triazole-3-carboxamide), effective against high hazard viruses such as Lassa fever, may produce hematological changes in some species. This study determined the extent of these changes in monkeys given a schedule of ribavirin treatment similar to that used in Lassa fever-infected patients. Drug was administered iv in a 33 mg/kg loading dose, followed by 17 mg/kg every 6 hr for 4 days, then 8 mg/kg every 8 hr for an additional 6 days; control monkeys received an equivalent volume of saline. Red blood cell counts decreased significantly by Day 6 but returned to pretreatment levels by the third week post-treatment. Hematocrits were reduced 30% by Day 7, reached their nadir on Day 11 with a mean value of 22%. Hemoglobin values dropped to 7–8 mg/dl, remained at that level for 10 days, and gradually returned to pretreatment levels. Three days after discontinuance of drug, reticulocytes increased then returned to control levels by Day 44. Platelet levels increased during treatment, peaked on Day 14, and then returned to baseline values. No significant changes were observed in total and differential WBC counts. Haptoglobin, SGOT, SGPT, total and direct bilirubin, BUN, blood glucose, and body weight were not altered. These data indicate that the proposed therapeutic regimen of ribavirin modifies the normal hemogram of rhesus monkeys. Observed effects appear to be fully reversible with hemograms returning to normal limits upon discontinuance of ribavirin. This effect is an important consideration in the treatment of Lassa fever in man.