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| 2. |
- Daly, AK, et al.
(författare)
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Nomenclature for human CYP2D6 alleles
- 1996
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Ingår i: Pharmacogenetics. - : Ovid Technologies (Wolters Kluwer Health). - 0960-314X. ; 6:3, s. 193-201
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Tidskriftsartikel (refereegranskat)
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| 3. |
- INABA, T, et al.
(författare)
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Pharmacogenetics in clinical pharmacology and toxicology
- 1995
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Ingår i: Canadian journal of physiology and pharmacology. - : Canadian Science Publishing. - 0008-4212 .- 1205-7541. ; 73:3, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- An international symposium entitled Pharmacogenetics in clinical pharmacology and toxicology: a tribute to Werner Kalow was held in Toronto, Ontario, July 20, 1994. This subject was particularly important to discuss in the presence of Werner Kalow, 77 years young, who is considered as one of the grandfathers of this unique combination of medical research fields. It has become increasingly appreciated that dozens of human drug metabolism polymorphisms exist. The interindividual variabilities in drug metabolism discussed at this symposium do not represent small differences such as 50% or 3-fold but, rather, represent 10- to greater than 1000-fold differences. When attributed to a single gene, dramatic differences can be seen among family members, just as blue and brown eyes can occur in siblings. These differences can result in acute drug toxicity. In addition, there are chronic effects: over one's lifetime, striking differences in the metabolism of drugs, occupationally hazardous chemicals, and other environmental pollutants can lead to interindividual differences in the buildup of DNA damage (e.g., mutations, chromosomal breaks, rearrangements) leading to toxicity and tumor initiation, as well as leading to a buildup in nongenotoxic signals (signal transduction pathways without DNA damage) important for toxicity, tumor promotion, and tumor progression. The human UDP glucuronosyltransferase (UGT superfamily is known to comprise more than 10 genes in humans, and probably in other mammalian species. Breakthroughs in UGT gene mutations responsible for the Crigler-Najjar syndrome and Gilbert's disease have recently been reported. The human cytochrome P450 termed CYP3A4 is a major P450 enzyme in the liver and gastrointestinal tract, and the full impact of the CYP3A4 polymorphism has yet to be fully appreciated. CYP3A4 metabolism of cyclosporin A, commonly prescribed to organ transplant recipients, the induction of CYP3A4 by rifampicin, and inhibition of CYP3A4 metabolism by erythromycin or ketoconazole are now quite well understood. The field of ethnopharmacology, or pharmacoanthropology, has recently emerged, pioneered at least in part by Kalow. Differences in debrisoquine–sparteine metabolism, S-mephenytoin hydroxylation, diazepam clearance, and omeprazole clearance in various Caucasian and Oriental subpopulations in a number of countries have been extensively reported. After a number of inconclusive studies, it has now been shown unequivocally that the human S-mephenytoin 4′-hydroxylase polymorphism represents at least two distinct mutations (one involving a splice site) in the CYP2C19 gene. Finally, the implications and clinical significance of a number of human polymorphisms (CYP2D6, CYP2C19, N-acetylation (NAT2), S-methylation by thiopurine methyltransferase (TPMT), and ester hydrolysis by plasma cholinesterase) were carefully reviewed at this symposium.Key words: pharmacology, toxicology, drug metabolism, pharmacogenetic polymorphism.
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| 6. |
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| 7. |
- Ingelman-Sundberg, M, et al.
(författare)
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Human cytochrome P-450 (CYP) genes: a web page for the nomenclature of alleles
- 2001
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 10:12, s. 1307-1308
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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