title: Pharmacokinetics of single-dose morinidazole in patients with severe renal impairment.
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 tmax of M4-1 differed greatly. Both AUC0-t and AUC0-∞ 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, t1/2 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Hong-yi
authors.initials: HY
authors.lastname: Tan
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Ji-shi
authors.initials: JS
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Guo-ping
authors.initials: GP
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D009593:Nitroimidazoles; C547405:morinidazole