Variations in demethylation of N-methylnaltrexone in mice, rats, dogs, and humans.
1. Rats and mice have a greater capacity than dogs or humans to N-demethylate the quaternary ammonium compound, N-methylnaltrexone. 2. In dogs, following the i.v. administration of N-[14C-methyl]methylnaltrexone, 50% of the radioactivity was excreted in the urine and an additional 30% in the faeces within 120 h. 3. In humans following the i.v. administration of 14C-N-methylnaltrexone, 40-60% of the radioactivity was excreted in the urine within the first 24 h. The plasma radioactivity-time curves indicated a biphasic decay and a short distribution phase between 6 and 9 min. with a longer elimination phase between 238 and 1320 min.
Kotake
A N
AN
Department of Pharmacological, University of Chicago, IL 60637.
Kuwahara
S K
SK
Burton
E
E
McCoy
C E
CE
Goldberg
L I
LI
D000368:Aged; D000818:Animals; D004285:Dogs; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D009292:Narcotic Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000644:Quaternary Ammonium Compounds; D051381:Rats; D013045:Species Specificity
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone