RT Journal Article
SR Electronic
T1 THE METABOLISM OF ISOCARBOXAZID (MARPLAN) IN THE RAT
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 157
OP 165
VO 130
IS 2
A1 Schwartz, Morton A.
YR 1960
UL http://jpet.aspetjournals.org/content/130/2/157.abstract
AB The synthesis of C14-isocarboxazid (Marplan) labeled in the benzyl moiety has been described. A 1 mg/kg intraperitoneal dose of C14-isocarboxazid has been found to be rapidly absorbed and distributed in the rat with the radioactivity reaching maximum tissue levels in 7.5 minutes. The fall-off of tissue radioactivity was characterized by a multi-component decline with the fast component exhibiting a half-life of approximately 30 minutes. The urinary radioactivity, which was virtually all accounted for as labeled hippurate, amounted to 75% of the dose in 24 hours. Secretion of radioactivity into the intestinal tract was also observed, with 7% of the dose found in the feces at the end of 24 hours. At a dose of 40 mg/kg of C14-isocarboxazid, 42.5% of the dose was excreted in the urine in 24 hours, and approximately 64% of this urinary radioactivity was present in hippurate. Fecal excretion of radioactivity amounted to 22% of the dose. The total excretion of radioactivity following equimolar doses of labeled isocarboxazid and iproniazid was found to be quantitatively similar after 1 day. However, analysis of the 6-hour excretion of radioactivity revealed that 45% of the iproniazid had been metabolized to pulmonary CO2 while 30% of the isocarboxazid was converted to urinary hippurate. The significance of these results in relation to monoamine oxidase inhibition and the detailed elucidation of the biological fate of isocarboxazid is discussed.