Biotransformation of an antihypertensive arylalkylamine analogue in the rat.
1. The excretion and metabolism of N-[2-(3,4-dimethoxyphenyl)ethyl]-5-methoxy-N,alpha-dimethyl-2-(phenyl ethynyl) benzenepropanamine (RWJ-26240) in the Wistar rat has been investigated after a single oral dose of 14C-RWJ-26240 (50 mg/kg free base). 2. Plasma samples were obtained for 24 h after dosing and urine and faecal samples were collected over 8 days, and they accounted for 0.9 and 96% of the dose, respectively. 3. Representative samples of plasma, urine and faecal samples were purified for metabolite isolation and identification using HPLC, tlc, mass spectra (CI and EI), 1H-NMR and derivatization. 4. Unchanged RWJ-26240 plus 11 metabolites were identified and accounted for > 80% of the sample radioactivity. 5. Four metabolic pathways for RWJ-26240 are proposed; namely (1) N-demethylation, (2) O-demethylation, (3) phenyl hydroxylation and (4) N-dealkylation. Pathways 1-3 appeared to be quantitatively more important.
Wu
W N
WN
Division of Preclinical Development, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
Masucci
J A
JA
Caldwell
G W
GW
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D008297:Male; D011437:Propylamines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014556:Urine / Q000737:chemistry
D000959:Antihypertensive Agents; D011437:Propylamines; C117299:RWJ 26240