Figure 3.

Simulated plasma colchicine concentrations (μg/l) versus time (h) in case of its co-administration with other medicines. (A) Co-administration with azithromycin (thus colchicine clearance would be reduced by 30%): Loading dose of 1 mg, followed then 0.5 twice daily, (B) Co-administration with lopinavir/ritonavir (thus colchicine clearance would be reduced by 70%): Loading dose of 0.5 mg and then after 72 h 0.5 mg every 72 h for 14 days or until discharge, (C) Co-administration with CYP3A4 inhibitors (e.g. diltiazem, imatinib, letermovir) [RECOVERY trial]: Loading dose of 1 mg, followed by 0.5 mg 12 h later, then maintenance dose 0.5 mg once daily. Upper line: 3 μg/l, plasma concentration that elicits toxic effects. Lower line: 0.5 μg/l, minimum effective plasma concentration. The inter-individual variability values, considered for all pharmacokinetic parameters, were those reported in the study of Thomas et al. (1989). Dashed lines indicate the average peak and trough concentration values at steady state.