Isolation and characterization of the urinary metabolites of arbaprostil in the male dog after intravenous administration.
The profile of urinary metabolites of 3H-arbaprostil was characterized in the male dog after intravenous administration. The major metabolites were purified and their structures deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivatives, aided by GC with simultaneous radioactivity monitoring. The identified metabolites accounted for 96% of the urinary excretion products. beta-Oxidation of the carboxy side-chain of arbaprostil to 15-methyl-2,3,4,5-tetranor PGE1, via the 15-methyl-2,3-dinor PGE2 intermediate, appeared to be the most significant metabolic pathway. In contrast to the rat, the following were observed in the dog: glucuronic acid conjugation of the 15-methyl-2,3,4,5-tetranor PGE, and PGA metabolites; detection of the 15-methyl-2,3-dinor PGE2 intermediate; absence of 19-hydroxyl-15-methyl-2,3,4,5-tetranor PGA, and PGB metabolites; oxidation at C-20; and excretion of some parent drug.
Thornburgh
B A
BA
Drug Metabolism Research, Upjohn Company, Kalamazoo, Michigan.
Shaw
S R
SR
Bronson
G E
GE
Sinha
A J
AJ
D000284:Administration, Oral; D000818:Animals; D001101:Arbaprostil / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D001711:Biotransformation; D002849:Chromatography, Gas; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D007275:Injections, Intravenous; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000652:urine*; D013237:Stereoisomerism
D011459:Prostaglandins E, Synthetic; D001101:Arbaprostil