CYP2A6 is a major catalyst of nicotine metabolism to cotinine. Previously, we demonstrated that the interindividual difference in nicotine metabolism is related to a genetic polymorphism of the CYP2A6 gene in Japanese. To clarify the ethnic differences in nicotine metabolism and frequencies of CYP2A6 alleles, we studied nicotine metabolism and the CYP2A6 genotype in 209 Koreans. The cotinine/nicotine ratio of the plasma concentration 2 h after chewing one piece of nicotine gum was calculated as an index of nicotine metabolism. The genotypes of CYP2A6 gene (CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4 and CYP2A6*5) were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism or allele specific (AS)-PCR. There were ethnic differences in the allele frequencies of CYP2A6*1A, CYP2A6*1B, CYP2A6*4 and CYP2A6*5 between Koreans (45.7%, 42.8%, 11.0% and 0.5%, respectively) and Japanese (42.4%, 37.5%, 20.1% and 0%, respectively, our previous data). Similar to the Japanese, no CYP2A6*2 and CYP2A6*3 alleles were found in Koreans. The homozygotes of the CYP2A6*4 allele (four subjects) were completely deficient in cotinine formation, being consistent with the data among Japanese. The heterozygotes of CYP2A6*4 tended to possess a lower metabolic ratio (CYP2A6*1A/CYP2A6*4, 4.79 +/- 3.17; CYP2A6*1B/CYP2A6*4, 7.43 +/- 4.97) than that in subjects without the allele (CYP2A6*1A/CYP2A6*1A, 7.42 +/- 6.56; CYP2A6*1A/CYP2A6*1B, 9.85 +/- 16.12; CYP2A6*1B/CYP2A6*1B, 11.33 +/- 9.33). The subjects who possess the CYP2A6*1B allele appeared to show higher capabilities of cotinine formation. It was confirmed that the interindividual difference in nicotine metabolism was closely related to the genetic polymorphism of CYP2A6. The probit plot of the metabolic ratios in Koreans (8.73 +/- 11.88) was shifted to a higher ratio than that in the Japanese (3.78 +/- 3.09). In each genotype group, the Korean subjects revealed significantly higher metabolic ratios than the Japanese subjects. The ethnic difference in cotinine formation might be due to environmental and/or diet factors as well as genetic factors.

Background: Bupropion is an antidepressant and a non-nicotine aid used in smoking cessation. It blocks the neuronal uptake of serotonin and norepinephrine and inhibits the neuronal reuptake of dopamine. Although several in vitro study demonstrated that CYP2D6 activity was inhibited by bupropion, there is no in vitro study that directly reports the inhibitory effects of bupropion on human major CYP isoforms. In the present study, we investigated the inhibitory effects and mechanism-based inactivation potencies of bupropion for human CYP2C19, CYP2D6, CYP2A6 and CYP3A4 activities. Methods: In vitro study was performed using microsomes from baculovirus-infected insect cells expressing specific human CYP isoforms. The specific activities for human CYP isoforms included in this study were S-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), testosterone 6-hydroxylation (CYP3A4), and coumarin 7-hydroxylation (CYP2A6). Results: Bupropion competitively inhibited S-mephenytoin 4'-hydroxylase (Ki = 1.631±0.544 μM) and bufuralol 1'-hydroxylase (Ki = 1.017±0.284 μM). The IC50 values for inhibition of CYP2C19 (coumarin, 1 μM) and CYP2D6 (bufuralol, 1 μM) index reaction by bupropion were 3.36 μM and 6.45 μM, respectively. CYP3A4 and CYP2A6 activities were not significantly inhibited by bupropion. Furthermore, bupropion did not reveal a mechanism-based inactivation of CYP2C19 and CYP2D6. It was clearly shown that CYP2C19 and CYP2D6 were not inactivated by bupropion in a time and concentration dependent manner. Conclusions: Bupropion showed inhibitory effects on CYP2C19 and CYP2D6 activities. These results suggest that bupropion would affect the pharmacokinetics of clinically used drugs that are metabolized by CYP2C19 and CYP2D6.

Clinical Pharmacology & Therapeutics (1999) 65, 127–127; doi:

Clinical Pharmacology & Therapeutics (1999) 65, 166–166; doi:

Background : The bioavailability of a generic preparation of aceclofenac (Omenol from Korea United Pharmaceutical Company) was evaluated in comparison with a proprietary product (Losec from Astra Pharmaceutical Company).Methods : Sixteen healthy male volunteers participated in the study conducted according to a two-way crossover, open-labeled Latin square design. The bioavailability was compared using the parameters total area under the plasma concentration-time curve (AUC0-∞ ), peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) Results : No statiscally significant difference was observed between the values of the two products in all three parameters. The difference of mean of AUC0-∞ and Cmax values of Omenol over those of Losec was found to lie between 8.05% and 2.49%, respectively, being within the acceptable bioequivalence limit of 20%.Conclusion : These findings indicate that the two preparations are comparable in the extent and rate of absorption.