• Archives of Pharmacal Research
• /
• v.6 no.1
• /
• pp.7-16
• /
• 1983

A methadone-diazepam interaction study in rats was performed in which conjugated metabolites of methadone were analyzed using deuterated biosynthetic internal standards. Diazepam (5mg/kg) was given to rats through a cannulate djugular vein and a subcutaneous dose of methadone (10mg/kg) was given. Bile was collecte through the cannulate dbile duct over a period of 24 hours. The deuterium label of the internal standards was found to be stable under conditions of the prolonged incubation. There was no significant difference in the excretion of the metabolites between the control and the diazepam treated rats. Feasibility of using biosynthetic internal standards with selected ion monitoring was established for the drug metabolism and kinetic studies.

• Toxicological Research
• /
• v.17
• /
• pp.145-155
• /
• 2001

Cytochrome P4502C19 (CYP2C19) is one of human polymorphic xenobiotic-metabolizing enzymes. The enzyme has been reported to catalyze more than 70 substrates, involving more than 100 reactions. These include several classes of therapeutic agents (e.g. anti-microbial. cardiovascular, psycho-active, etc.), sex hormones and insecticides. Associations of the CYP2C19 genotype/phenotype with individual differences in drug efficacy (e.g. diazepam, omeprazole, proguanil) and toxicity (e.g. mephenytoin, barbiturates) have been documented by many investigators. At least 11 allelic variants of CYP2C19 gene were reported to date. Most of the mutant alleles found in the poor metabolizer (PM) led to the production of truncated and/or inactive proteins. Except for the exon 6, single-nucleotide mutations were reported in all nine exons of the gene. Genetic polymorphism of CYP2C19 shows marked interethnic variation with the population frequencies of PM phenotype ranging from 1∼2% up to more than 50%. The prevalence of CYP2C19 PM tends to be higher in Asian and certain Pacific Islanders than other race or ethnic specificity. Genotyping results of CYP2C19 also revealed that there are different proportions of individual mutant alleles among ethnic populations. This may, in part, explains the interethnic difference in the metabolism of certain drugs (i.e. diazepam), though they were from the same CYP2C19 phenotype. Recently, our research group has studied the genotype and phenotype of CYP2C19 and found that the PM frequency (7∼8%) in Thais is lower than other Asian populations. Molecular and clinical impacts of this finding warrant to further investigation.

• Advances in Traditional Medicine
• /
• v.7 no.4
• /
• pp.357-362
• /
• 2007

Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme involved in the metabolism of therapeutic drugs, including (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals are characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasians, but in 18-23% of Asians. To clarify the association between CYP2C19 polymorphisms and gastric cancer in Koreans, we investigated CYP2C19 genotypes ($CYP2C19^*1,\;{^*2},\;and\;^*3$) in 109 patients with gastric cancer and 211 controls. Normal ($CYP2C19^*1$) and defective alleles were detected with polymerase chain reaction/restriction enzyme analysis. CYP2C19 has three hereditary genotypes: homozygous EM, with high enzymatic activity; heterozygous EM, with moderate enzymatic activity; and PM, with no enzyme activity. We found that CYP2C19 heterozygous EM is more closely associated with gastric cancer than is homozygous EM. Because the CYP2C19 genotype varies in Koreans, a genotyping test is desirable to prevent gastropathy recurrence in patients before their doses of omeprazole are reduced during maintenance therapy.

• Korean Journal of Clinical Pharmacy
• /
• v.15 no.2
• /
• pp.149-159
• /
• 2005

Purpose: To determine the extent and rate of prescription drug therapy, especially polypharmacy and the prevalence of potentially inappropriate medication use in Korean elderly ambulatory patients based on an explicit criterion. Methods: Performed a retrospective study of 65 years or older ambulatory patients visiting a university hospital based clinic from January 2002 to April 2004. Study determined the patterns of drug prescription per Anatomical Therapeutic Chemical Classification and the potentially inappropriate medication usage based on explicit Beers criteria. Results: Of the 4,042 elderly patients the mean number of prescription was $2.2{\pm}2.0$, which was similar between genders and all age groups within the elderly. 10.7% of patients were prescribed with more than 5 medications concurrently. The most frequently prescribed medication was the drugs used for treating nervous system diseases (44.3%), followed by alimentary tract/metabolism disorders (27.6%), cardiovascular disease (10.7%), blood/blood forming disorders (4.3%), respiratory disorders (6.5%), and musculoskeletal diseases (3.2%). A total of 511 elderly (13%) was prescribed with medication that met the criteria for=1 potentially inappropriate drugs for the elderly. This proportion was similar between genders and all age groups within the elderly. Among these 511 elderly patients the mean number of potentially inappropriate drugs prescribed was $5.1{\pm}3.3$ drugs. Potentially inappropriately prescribed drugs included amitriptyline (76 cases), diazepam (69 cases), ketorolac (57 cases), short acting nifedipine (44 cases), triazolam (38 cases), and hydroxyzine (38 cases). Conclusion: Potentially inappropriate drug prescribing in Korean ambulatory elderly patients are common. Education programs and interventions aimed at optimizing the prescribing and dispensing of the most appropriate drugs are needed.