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R D Smyth

Publications and source records attributed to R D Smyth.

70 records · Page 4Linked to original sources
PubMedDate not supplied

Comparative metabolism of fenclorac in rat, dog, monkey, and man.

Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis.

Administration, Oral↗
PubMedDate not supplied

Disposition of parenteral butorphanol in man.

The metabolism and elimination of 3H-butorphanol (levo-3, 14-dihydroxy-N-(cyclobutylmethyl)[15-3H]morhinan) tartrate were determined in man after therapeutic im (2 mg) and iv (1 mg) doses. As judged from urinary excretion of radioactivity, the im dose was completely absorbed. Butorphanol was rapidly distributed to tissues, had a plasma half-life of about 3 hr, and was extensively metabolized prior to elimination. The major route of elimination was renal, with fecal excretion being a minor route. Hydroxybutorphanol [3, 14-dihydroxy-N-(trans-3'-hydroxycyclobutylmethyl)morphinan] was isolated and identified as a major urinary metabolite and was also present in the plasma. The disposition of butorphanol is compared and contrasted to the disposition of morphine and pentazocine.

Adult↗