Pharmacokinetics of single-dose morinidazole in patients with severe renal impairment

Objective: To evaluate the pharmacokinetics of morinidazole in individuals with severe renal impairment (RI). Methods: This open-label Phase I study enrolled healthy volunteers and patients with severe RI aged 18 - 65 years. All subjects received a single infusion of sodium chloride injection with 500 mg morinidazole. Plasma and urine concentration of morinidazole and one of its metabolites (M4-1) were evaluated by using HPLC-UV and HPLC-MS/MS respectively. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 6 0 software. Results: 22 individuals (healthy: n = 11, severe RI: n = 11) received morinidazole. In both groups, maximum plasma concentration of morinidazole was reached within 1 hour, while the t(max) of M4-1 differed greatly. Both AUC(0-t), and AUC(0-infinity) of morinidazole were 1.4 times higher in patients with severe RI, while M4-1 were over 7 times higher than healthy groups. Renal excretion of unchanged morinidazole was decreased by 65% in patients with RI, and M4-1 was decreased by 72%. Apparent correlation between CLcr and CL, AUC, t(1/2) and CLr were seen in two groups. Conclusions: A single dose of 500 mg morinidazole is well tolerated. Changes in pharmacokinetic parameters of morinidazole and M4-1 are seen in patients with RI and may be clinically important.