Poor metabolizer

Cytochrome P450 2C19 Deficient activity in about 3% of Caucasian populations and in about 20% of Asian populations. Prolonged action of several CYP2C19 inactivated drugs like omeprazole or diazepam in the poor metabolizers. 

Cytochrome P450 2D6 Extremely high activity in about 2% of Caucasian populations and completely deficient activity in about 7%. Inefficiency in ultrarapid metabolizers and extremely heavy effects in poor metabolizers for more than 50 drugs. A few drugs requiring bioactivation by CYP have low efficacy in poor metabolizers (example codein is activated to morphine via CYP2D6). 

Poor Metabolizer Phenotype Population Pharmacokinetics Positron Emission Tomography Post-translational Modification Potassium Channels Potassium Competitive Acid Blockers PP... 

There are many sweeteners available today. Some are nutritive sweeteners, such as sugar others are non-nutritive, such as saccharin and still others fall somewhere in between, as they may have fewer calories than sugar, or be poorly metabolized in the body,... 

When assayed in HEK293 cells transfected with the cloned human, rat and guinea pig TRPVl, (23a) showed similar potencies. Not unexpeetedly, (23a) showed poor metabolic stability and a structure-activity study to optimize potency and drug-like properties was initiated. Modification on the left-handed A -aryl section showed that ... 

If a patient has renal or hepatic impairment or a poor metabolizer genotype, adjust chemotherapy doses if necessary. 

Goldstein, J. A., Ishizaki, T. etal. (1997). Frequencies ofthe defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics, 7(1), 59-64. 

Hamelin, B. A., Turgeon, J., Vallee, F. etal. (1996). The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin. Pharmacol. Ther., 60, 512-21. 

Cartwright [124] reported that miconazole was slightly absorbed from epithelial and mucosal surface. The drug is well absorbed from the gastrointestinal tract, but caused nausea and vomiting in some patients. The drug may be given intravenously but was associated phlebitis. Up to 90% of the active compound was bound to plasma protein. Distribution into other body compartments was poor. Metabolism was primarily in the liver, and only metabolites were excreted in the urine. At therapeutic levels, they were relatively nontoxic both locally and systematically, but occasionally produced disturbances on the central nervous system. 

CYP2C9 Multiple allelic variants of CYP2C9 may account for the occurrence of poor metabolizers and increased efficacy of warfarin (84)... 

Ibeanu GC, Blaisdell ], Ferguson R], Ghanayem Bl, Brosen K, Benhamou S et al. A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-me-phenytoin. J Pharmacol Exp Ther 1999 290[2] 635—640. 

---