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In vitro inhibition studies of two isozymes of human liver cytochrome P-450. Mephenytoin p-hydroxylase and sparteine monooxygenase.
Abstract
Human liver preparations were used to screen various drugs for their capability of binding to mephenytoin p-hydroxylase and sparteine monooxygenase, two cytochrome P-450-catalyzed activities that are independently heritable. For this screening, any indication of competitive inhibition by the drug was interpreted as an indication of binding. Among 64 drugs and alkaloids tested, 24 compounds caused inhibition of mephenytoin p-hydroxylation but the inhibition was weak in most cases; by contrast, 40 of the 64 compounds inhibited sparteine oxidation, the inhibition being potent in many cases. The only fairly strong inhibitors of mephenytoin p-hydroxylation were the alkaloid papaverine and the monoamine oxidase inhibitors tranylcypromine and nialamide. The results of these inhibition studies confirm the independence of the two monogenic defects observed in different populations. Metabolism is possibly altered in poor metabolizers of mephenytoin with fewer drugs than in poor metabolizers of sparteine.
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Citations
Cited by
Clinical Significance of the Cytochrome P450 2C19 Genetic Polymorphism
Desta, Z., Zhao, X., Shin, J.-G., & Flockhart, D. A. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241120-00002 · Cited by 942
Clinical Pharmacology of MAO Inhibitors: Safety and Future
Yamada, M. (2004) · NeuroToxicology · doi:10.1016/s0161-813x(03)00097-4 · Cited by 324
Genetic polymorphism of S-mephenytoin hydroxylation
Wilkinson, G. R., Peter Guengerich, F., & Branch, R. A. (1989) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(89)90047-8 · Cited by 292
Pharmacokinetics of Haloperidol
Froemming, J. S., Lam, Y. W. F., Jann, M. W., & Davis, C. M. (1989) · Clinical Pharmacokinetics · doi:10.2165/00003088-198917060-00004 · Cited by 291
Clinical significance of the sparteine/debrisoquine oxidation polymorphism
Br�sen, K., & Gram, L. F. (1989) · European Journal of Clinical Pharmacology · doi:10.1007/bf00637732 · Cited by 282
Metadata
- Authors
- Inaba, T., Jurima, M., Mahon, W. A., & Kalow, W.
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 1985-07
- Volume
- 13
- Issue
- 4
- Pages
- 443-448
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W2410779580
- Cited by
- 179
- References
- 0
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- closed
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- Inaba, T., Jurima, M., Mahon, W. A., & Kalow, W. (1985). In vitro inhibition studies of two isozymes of human liver cytochrome P-450. Mephenytoin p-hydroxylase and sparteine monooxygenase. Drug Metabolism and Disposition. https://doi.org/10.1016/s0090-9556(25)08231-5
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