Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens

Colchicine is widely investigated for cardioprotection of COVID-19 patients since it can prevent the phenomenon of 'cytokine storm' and may reduce the complications arising from COVID-19. Despite the potentially beneficial effects of colchicine, there is no consensus on the appropriate dosage regimen and numerous schemes are currently used. In this study, simulations were performed to identify the ability of dosage regimens to attain plasma levels in CVOID-19 patients, known to be generally safe and efficacious. Since renal and hepatic impairment, as well as, drug-drug interactions have been identified to be the most significant factors increasing colchicine toxicity, the impact of these interactions was assessed in the simulations. Some dosage regimens lead to high colchicine concentrations, while others result in sub-therapeutic levels. Additional dosage schemes were proposed in this study aiming to be applied in patients with clearance insufficiency. Colchicine administration of 0.5 mg twice daily, can be considered safe and effective. In cases of clearance impairment, doses as low as 0.25 mg thrice or twice daily should be applied. Colchicine is a narrow therapeutic index drug and dosage regimens tailored to patients' needs should be designed.