The metabolism of ribavirin in erythrocytes and nucleated cells

Abstract

1. The metabolism of the broad-spectrum antiviral drug ribavirin was examined in intact human erythrocytes, cultured skin fibroblasts and EBV-transformed lymphoblasts. At an extracellular ribavirin concentration of 35 microM all the cell types produced ribavirin mono-, di- and triphosphate, with the nucleotide concentration reaching half-maximum in 210, 245 and 267 min for fibroblasts, lymphoblasts and erythrocytes, respectively. The ratio of mono-, di- and triphosphates was ca 4:1:40 in fibroblasts, 3:1:8 in lymphoblasts and 1:5:17 in erythrocytes. 2. When ribavirin was removed from the medium, the half-life of ribavirin nucleotides was less than 2 hr in fibroblasts and lymphoblasts, but greater than 24 hr in erythrocytes. 3. In energy-starved erythrocytes, the catabolism of ribavirin nucleotides closely followed the catabolism of adenine nucleotides. 4. None of these cell types excreted appreciable amounts of the ribavirin catabolites triazole carboxamide, triazole carboxylate or triazole carboxylate ribonucleoside. 5. Cells deficient in adenosine kinase produced greater than 4% of the ribavirin nucleotides of normal controls. 6. The nucleated cells quickly hydrolyzed ribavirin 5'monophosphate to ribavirin, whereas this activity was negligible in erythrocytes.