Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus

BackgroundTacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus. MethodThis study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three-d washout period, plasma colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24h post-dose of 1mg oral colchicine. Area under the curve 0-24h (AUC(0-24)) and maximum concentration (C-max) were evaluated and compared between the groups. ResultsColchicine AUC(0-24) was six-fold higher in HD (p<0.001) and three-fold higher in KTx recipients (p<0.001) when compared to the control. The low GFR group had mildly higher AUC(0-24) than the control group. C-max levels were also higher in HD (p=0.011) and KTx recipient (p=0.06) groups and mildly elevated in low GFR patients in comparison with controls. ConclusionColchicine AUC(0-24) and C-max were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances.