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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.

Publication ,  Journal Article
Zbaida, S; Du, Y; Shannon, D; Laudicina, D; Thonoor, CM; Ng, K; Blumenkrantz, N; Patrick, JE; Cayen, MN; Friary, R; Seidl, V; Chan, TM ...
Published in: Biopharmaceutics & drug disposition
July 1998

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzol[b][1,8]naphthyrid in-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.

Duke Scholars

Published In

Biopharmaceutics & drug disposition

DOI

EISSN

1099-081X

ISSN

0142-2782

Publication Date

July 1998

Volume

19

Issue

5

Start / End Page

315 / 332

Related Subject Headings

  • Species Specificity
  • Rats, Sprague-Dawley
  • Rats
  • Psoriasis
  • Pharmacology & Pharmacy
  • Naphthyridines
  • Male
  • Macaca fascicularis
  • Liver
  • In Vitro Techniques
 

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Zbaida, S., Du, Y., Shannon, D., Laudicina, D., Thonoor, C. M., Ng, K., … McPhail, A. T. (1998). 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. Biopharmaceutics & Drug Disposition, 19(5), 315–332. https://doi.org/10.1002/(sici)1099-081x(199807)19:5<315::aid-bdd107>3.0.co;2-n
Zbaida, S., Y. Du, D. Shannon, D. Laudicina, C. M. Thonoor, K. Ng, N. Blumenkrantz, et al. “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.Biopharmaceutics & Drug Disposition 19, no. 5 (July 1998): 315–32. https://doi.org/10.1002/(sici)1099-081x(199807)19:5<315::aid-bdd107>3.0.co;2-n.
Zbaida, S., et al. “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.Biopharmaceutics & Drug Disposition, vol. 19, no. 5, July 1998, pp. 315–32. Epmc, doi:10.1002/(sici)1099-081x(199807)19:5<315::aid-bdd107>3.0.co;2-n.
Zbaida S, Du Y, Shannon D, Laudicina D, Thonoor CM, Ng K, Blumenkrantz N, Patrick JE, Cayen MN, Friary R, Seidl V, Chan TM, Pramanik B, Spangler M, McPhail AT. 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. Biopharmaceutics & drug disposition. 1998 Jul;19(5):315–332.
Journal cover image

Published In

Biopharmaceutics & drug disposition

DOI

EISSN

1099-081X

ISSN

0142-2782

Publication Date

July 1998

Volume

19

Issue

5

Start / End Page

315 / 332

Related Subject Headings

  • Species Specificity
  • Rats, Sprague-Dawley
  • Rats
  • Psoriasis
  • Pharmacology & Pharmacy
  • Naphthyridines
  • Male
  • Macaca fascicularis
  • Liver
  • In Vitro Techniques