Pharmacokinetic study of modafinil in relation to gender and ethnicity in healthy young Chinese volunteers.

PURPOSE: Pharmacokinetics of modafinil were investigated in relation to sex and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui (n = 10/group) following administration of a single 200 mg oral dose. METHODS: Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by HPLC. Pharmacokinetic parameters were evaluated using noncompartmental methods. RESULTS: Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (C(max)) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC(0-∞)), were higher in women compared to men (p < 0.01). No sex-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and t1/2 were found to exhibit ethnicity-based significant differences. CONCLUSION: There are pharmacokinetic differences based on sex and ethnicity for modafinil.

Pharmacokinetics of Tinidazole in Chinese subjects: comparison of Mongolian, Korean, Hui, Uighur and Han nationalities.

PURPOSE: This study investigated the pharmacokinetics of tinidazole in subjects of five different Chinese nationalities (Han, Mongolian, Korean, Hui, and Uighur). METHODS: Fifty healthy subjects (five male and five female of each nationality) were recruited for the study, and each received 1 g tinidazole. A total of 14 blood samples were collected over a 72-hour period after administration. RESULTS: Pharmacokinetic profiles, including area under the curve from time zero to infinity (AUC0-inf), peak plasma concentration (Cmax), time to reach Cmax (tmax), oral clearance (CL/F), elimination rate constant (Ke), and elimination half-life (t1/2), were determined following a single oral dose of tinidazole. The respective pharmacokinetic properties of Han, Mongolian, Korean, Hui, and Uighur nationalities were: half-life (h): 16.94+/-2.40, 16.40+/-1.79, 16.63+/-1.82, 16.81+/-1.56, 14.34+/-1.92; Cmax (microg/mL): 19.04+/-2.42, 19.22+/-4.93, 20.83+/-3.33, 20.25+/-4.05, 18.81+/-3.10; AUC0-inf (h*microg/mL): 483.13+/-65.65, 479.70+/-99.74, 511.07+/-53.47, 514.25+/-130.78, 388.58+/-37.37. The t1/2 and AUC0-inf of Uighur subjects were significantly lower (p =0.023, 0.011) and the CL/F and Ke were significantly higher (p = 0.003, 0.013) than those of other nationalities. After normalization by weight, the differences in AUC0-inf and CL/F between Uigur subjects and those of other races were still significant. CONCLUSIONS: The results indicate that ethnicity had significant impact on the pharmacokinetics of tinidazole after a single oral dose in healthy volunteers of different nationalities in China.

Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese populations.

PURPOSE: This study was carried out to estimate the allele and genotype frequencies of common variants in the CYP3A4, CYP2C19, and CYP2D6 in the Han, Uighur, Hui, and Mongolian Chinese populations and compare genetic polymorphisms difference between the Han and minority Chinese ethnicities. METHODS: We evaluated 672 unrelated, healthy Chinese volunteers (Han: 136; Uighur: 214; Hui: 164; Mongolian: 158). Genomic DNA was extracted from peripheral leukocytes and genotyped for CYP3A4*18, CYP2C19*2, *3, and CYP2D6*10 by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The allele frequencies of CYP3A4*18 in the Han, Uighur, Hui, and Mongolian Chinese population were 18.4%, 14.0%, 19.2%, and 20.3%, respectively; the allele frequencies of CYP2C19*2 were 38.6%, 32.5%, 49.4%, and 41.5%, respectively; the allele frequencies of CYP2C19*3 were 5.2%, 2.1%, 5.2%, and 4.4%, respectively; and the allele frequencies of CYP2D6*10 were 57.4%, 22.4%, 39.7%, and 46.5%, respectively. CONCLUSION: The results showed that there was no significant ethnic difference in the distribution of CYP3A4*18 and CYP2C19*3 genotypes in the Han, Uighur, Hui, and Mongolian Chinese populations. For CYP2C19*2, the Han were not significantly different from the Uighur, Hui, or Mongolian; however, the Uighur were significantly lower than the Hui and the Mongolian, and the Mongolian were significantly lower than the Hui. For CYP2D6*10, the Mongolian were not significantly different from the Han and the Hui. However, the Uighur were significantly lower than the other three. Our findings confirm the existence of interethnic differences in the CYP2C9, CYP2C19, and CYP2D6 alleles and genotype frequencies in the Han, Uighur, Hui, and Mongolian Chinese populations.