PT  - JOURNAL ARTICLE
AU  - Manna Temesvári
AU  - László Kóbori
AU  - József Paulik
AU  - Enikő Sárváry
AU  - Ales Belic
AU  - Katalin Monostory
TI  - Estimation of Drug-Metabolizing Capacity by Cytochrome P450 Genotyping and Expression
AID  - 10.1124/jpet.111.189597
DP  - 2012 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 294--305
VI  - 341
IP  - 1
4099  - http://jpet.aspetjournals.org/content/341/1/294.short
4100  - http://jpet.aspetjournals.org/content/341/1/294.full
SO  - J Pharmacol Exp Ther2012 Apr 01; 341
AB  - Many undesired side effects or therapeutic failures of drugs are the result of differences or changes in drug metabolism, primarily depending on the levels and activities of cytochrome P450 (P450) enzymes. To assess whether P450 expression profiles can reflect hepatic drug metabolism, we compared P450 mRNA levels in the liver or peripheral leukocytes with the corresponding hepatic P450 activities. A preliminary P450 genotyping for the most frequent polymorphisms in white populations (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, CYP2D6*6, and CYP3A5*3) was carried out before P450 phenotyping, excluding the donors with nonfunctional alleles of CYP2C9, CYP2C19, and CYP2D6 and those with a functional CYP3A5*1 allele from a correlation analysis. The hepatic mRNA levels of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 displayed a strong association with P450 activities in the liver, whereas the expression of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in leukocytes was proven to reflect the hepatic activities of these P450 species. The leukocytes were found to be inappropriate cells for the assessment of hepatic CYP2B6 and CYP2D6 activities. Combining the results of P450 genotyping and phenotyping analyses, patients' drug-metabolizing capacities can be estimated by the P450 expression in the liver and in leukocytes with some limitations. Patients' genetic and nongenetic variations in P450 status can guide the appropriate selection of drugs and the optimal dose, minimizing the risk of harmful side effects and ensuring a successful outcome of drug therapy.