Abstract

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–∞ 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 CL_cr and CL, AUC, t_1/2 and CL_r 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.

Author Details

Authors

• Hao Zhang²
• Lu Huang¹,³
• Yuan-yuan Huang¹
• Bin Yi²
• Qi Pei¹
• Hong-yi Tan¹
• Jie Huang¹
• Ji-shi Liu²
• Hong Yuan¹
• Guo-ping Yang¹

Departments

• ¹ Center of Clinical Pharmacology,
• ² Department of Nephrology, the Third Xiangya Hospital, and
• ³ College of Pharmacy, Central South University, Changsha, Hunan, China

Address

Prof. Guoping Yang
Center of Clinical Pharmacology, Third Xiangya Hospital
Central South University
Changsha, Hunan 410013, China
Email: [email protected]

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