Metabolism and disposition of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide Hcl (LY 195448) in rodents.
The disposition and metabolism of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide HCl, or LY 195448 (LY), were studied in rodents 1 hr following a single iv injection of 14C-LY at 30 mg/m2 (10 mg/kg mice and 5 mg/kg rats), In all tissues and carcases, recovery of 14C was nearly complete. The majority of radioactivity was recovered from intestine (40%) whereas liver and urine accounted for 10% each, kidney for 3-5%, and plasma for 1-3% of total administered radioactivity. Analyzing by HPLC and TLC, para-hydroxy-LY (para-OH-LY) in addition to unchanged drug, was found in all tissues. Meta-OH-LY was detected only in urine, intestine and kidney. These metabolites were found to be conjugated with either glucuronide or sulfate moieties. Peaks coeluting with authentic para-OH-meta-methoxy-LY and di-OH-LY were also observed.
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University of Texas M.D. Anderson Cancer Center, Department of Medical Oncology, Houston 77030.
Covington
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WP
Lin
J
J
Brown
N S
NS
Newman
R A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D001549:Benzamides / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004285:Dogs; D004983:Ethanolamines / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013429:Sulfatases / Q000378:metabolism; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D001549:Benzamides; D004983:Ethanolamines; D009097:Multienzyme Complexes; C023059:glusulase; C060459:4-(3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl)benzamide; D013429:Sulfatases; D005966:Glucuronidase