Prediction of Pharmacokinetics and Efficacy/Toxicity by Genotypes of Metabolic Enzymes

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N-acetyltransferase 2 (NAT2) and cytochrome P450 2C19 enzymes are known to exhibit a hereditarily determined polymorphism. The characterization of genetic variation at the DNA level for these enzymes has made it possible to determine an individual genotype. The common method is a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method using blood samples. We have developed a novel method for determining the NAT2 and CYP2C19 genotypes using genomic DNA extracted from single hairs, buccal cells and fingernail.The N-acetylation activity for procainamide, isoniazid (INH) and sulfapyridine (SP) was well correlated with NAT2 genotype in healthy volunteers study. Urinary excretion ratios of AcINH and INH in tuberculous patients and plasma concentration of AcSP and SP in ulcreative colitis also showed the same values in each NAT2 genotype as normal subjects. Therefore, NAT2 genotype is the main factor which effect on the metabolism of these drugs compared with coadministration drugs or hepatic and renal functions. Furthermore, we have first found that anti-Helicobacter pylori efficacy of omeprazole can be related to the CYP2C19 genotype, that is, the eradication effect of omeprazole with amoxicillin was highly efficient in CYP2C19 poor metabolizers, suggesting that clarithromycin or metronidazole needs not to be used for this group on the first line therapy. Genotyping by PCR-RFLP,which is a simple in vitro test, can provide a new strategy to choose an optimal regimen based upon the individual genotype.