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

ABSTRACT

BACKGROUND: Tacrolimus 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. METHOD: This 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 24 h post-dose of 1 mg oral colchicine. Area under the curve 0-24 h (AUC0-24 ) and maximum concentration (Cmax ) were evaluated and compared between the groups. RESULTS: Colchicine AUC0-24 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 AUC0-24 than the control group. Cmax 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. CONCLUSION: Colchicine AUC0-24 and Cmax were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances.