For patients with chronic hepatitis C virus (HCV), chlorcyclizine HCl plus ribavirin showed some anti-HCV effects, according to results published in Antiviral Research.

The results indicated that the dose used in the study may be subtherapeutic in humans, and the researchers recommend further studies with different iterations of chlorcyclizine HCl.

The study included participants with chronic HCV (n=24). Participants were randomly assigned to receive chlorcyclizine HCl (75 mg twice daily) or chlorcyclizine HCl plus weight-based ribavirin (1000/1200 mg daily) for 28 days. Participants began therapy with a loading dose of chlorcyclizine HCl 150 mg ± ribavirin. The researchers performed serial assessments of safety, pharmacokinetic markers, and viral kinetic markers and did liver testing.

At the end of therapy, participants treated with chlorcyclizine HCl monotherapy did not have a significant or sustained reduction in viremia (P =.69). However, 58% (7/12) of those treated with chlorcyclizine HCl + ribavirin had a >3-fold decline in HCV RNA.

In participants who responded to therapy, 2 had monophasic, 2 had biphasic, and 3 had triphasic viral kinetic responses.

Unlike established ribavirin monotherapy response, participants taking chlorcyclizine HCl + ribavirin showed a continued viral decline, which the researchers believe may indicate a synergistic effect of this combination treatment.

Using mathematical modeling, the researchers predict that chlorcyclizine HCl + ribavirin will have a median effectiveness of 59% in blocking viral production and 78% in blocking infection.

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“Our recent structure-activity relationship campaign has generated several [chlorcyclizine HCl] derivatives that are more potent and have more optimal pharmacokinetic features,” the researchers wrote. “These improved compounds may be more suitable for further human testing and therapeutic development.”

Reference

Koh C, Dubey P, Han MAT, et al. A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C. Antiviral Res. 2019;163:149-155.