A specific enzyme immunoassay (EIA) with selective extraction for quantitation of a topical anti-inflammatory agent, SCH 40120, in human plasma

Wang, Changjin; Tian, Zuguang; Reyes, Virginia; Lin, Chin‐Chung

doi:10.1016/0731-7085(94)00111-e

Cited by 2 publications

(1 citation statement)

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“…Isolation attempts using dilute clinical samples unsurprisingly afforded no drug-related metabolite specimens sufficient in quantity and purity for identification. No synthetic samples of genuine metabolites were available when the clinical work was done, although samples of certain putative metabolites did aid efforts to exclude structures [11,12]. For example, the samples included 40120 derivatives hydroxylated in the pyridine or chlorophenyl rings.…”

Section: Introductionmentioning

confidence: 99%

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

Zbáida¹,

Du²,

Shannon³

et al. 1998

Biopharm. Drug Dispos.

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The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10‐(3‐chlorophenyl)‐6,8,9,10‐tetrahydrobenzol[b][1,8]naphthyridin‐5(7H)‐one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6‐, 7‐, and 9‐carbinols, the glucuronide of the 6‐carbinol, and the 6‐ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non‐physiological ratio of substrate to liver, the 6‐carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6‐ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6‐carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample. © 1998 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%