Assessment of conception periods for patients treated with nucleoside analogues based on their intracellular accumulation in erythrocytes.

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Ribavirin (RBV), a nucleoside analogue, for hepatitis C virus (HCV) eradication requires the patients to have contraception for 6 months after stopping the therapy because of possible deformity caused by RBV. This period is enough to remove plasma RBV with the half-life (T1/2) of 12 days. Intracellular RBV, which is accumulated as the phosphorylated RBV in the tissue including erythrocytes, may require much time to be removed. Plasma and whole blood concentration of RBV were monitored before and after stopping the interferon (IFN)/RBV therapy in 45 HCV patients. Mean plasma and whole blood RBV were 10.1±4.6 and 307.9±146.5 μM, respectively, when IFN/RBV therapy was stopped. The T1/2 for plasma and whole blood RBV were 12.9±4.4 and 23.9±7.5 days, respectively. It was estimated that 79 (51-121) and 176 (130-331) days were required for removing RBV from plasma and whole blood, respectively. Population pharmacokinetic analysis for whole blood RBV revealed that 6 months was not enough for removing RBV from blood in 33% of HCV patients. Six months may not be enough as the contraception period after stopping RBV in patients with longer T1/2 of whole blood RBV.