Pharmacokinetic Disposition Difference Between Cyclosporine and Voclosporin Drives Their Distinct Efficacy and Safety Profiles in Clinical Studies

Clinical Pharmacology : Advances and Applications
Yan LiSimon Zhou

Abstract

Voclosporin, a more potent derivative of cyclosporine, has been studied extensively in patients with immunologic disorders such as psoriasis, organ transplantation, uvetitis and lupus nephritis. Although better tolerated and safer than cyclosporine, voclosporin is inferior to cyclosporine in treating psoriasis, non-inferior to tacrolimus in organ transplantation and efficacious in treating lupus nephritis. The pharmacokinetic dispositions of voclosporin and cyclosporine in central and peripheral compartments were analyzed and correlated with their distinct clinical efficacy and safety profiles. Both drugs demonstrated non-linear pharmacokinetics with increasing doses, more prominently at lower doses of voclosporin than at 10-fold higher doses of cyclosporine. Repeated lower dosing of voclosporin produced preferential calcineurin inhibition in and near blood circulation, leading to relatively lower cardiovascular and renal adverse effects but inferior efficacy for psoriasis compared to cyclosporine. With 10-fold higher plasma levels and deeper tissue penetration, cyclosporine has more prevalent renal and cardiac toxicities but superior efficacy to treat psoriasis. Although the two drugs are similar in structure and mechanism of ...Continue Reading

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