Effects of Renal Impairment on the Pharmacokinetics of Morinidazole: Uptake Transporter-Mediated Renal Clearance of the Conjugated Metabolites

• Published in: Antimicrobial agents and chemotherapy Vol. 58; no. 7; pp. 4153 - 4161
• Main Authors: Zhong, Kan, Li, Xiuli, Xie, Cen, Zhang, Yifan, Zhong, Dafang, Chen, Xiaoyan
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.07.2014
• Subjects: Adult; Anti-Bacterial Agents; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - urine; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Biological and medical sciences; Cell Line; Cimetidine - pharmacology; Female; HEK293 Cells; Humans; Infusions, Intravenous; Kidney - metabolism; Male; Mechanisms of Action: Physiological Effects; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nitroimidazoles; Nitroimidazoles - blood; Nitroimidazoles - pharmacokinetics; Nitroimidazoles - urine; Organic Anion Transport Protein 1; Organic Anion Transport Protein 1 - genetics; Organic Anion Transport Protein 1 - metabolism; Organic Anion Transporters, Sodium-Independent; Organic Anion Transporters, Sodium-Independent - genetics; Organic Anion Transporters, Sodium-Independent - metabolism; Pharmacology. Drug treatments; Probenecid - pharmacology; Protein Binding; Renal failure; Renal Insufficiency; Renal Insufficiency - metabolism; Transfection; Young Adult; Kidney disease; Urinary system disease; Nephropathy; Metabolite; Renal failure; Clearance; Pharmacokinetics; Uptake; Carrier protein; Kidney

Morinidazole is a novel 5-nitroimidazole antimicrobial drug that undergoes extensive metabolism in humans via N + -glucuronidation ( N + -glucuronide of S -morinidazole [M8-1] and N + -glucuronide of R -morinidazole [M8-2]) and sulfation (sulfate conjugate of morinidazole [M7]). Our objectives were...