Comparative pharmacokinetics of zolpidem tartrate in five ethnic populations of China.

The objective of this study was to evaluate the difference in the pharmacokinetics of zolpidem tatrate in subjects from five Chinese ethnicities (Han, Mongolian, Uigur, Korean and Hui). Healthy subjects (10 Hans, 10 Mongolians, 10 Uigurs, 10 Koreans and 9 Huis) were recruited and each received a 10 mg tablet-dose of zolpidem tatrate. A total of 12 plasma samples were collected over a 12 h period after administration. The concentrations of zolpidem in plasma were determined by an HPLC-FLU method, after which the pharmacokinetic parameters were determined using DAS 2.0 software and analyzed by SPSS 16.0 software. After normalization by weight, no differences were noted in the pharmacokinetic parameters of zolpidem tatrate among the five ethnic groups (P>0.05). However, there were statistically significant differences between males and females for the pharmacokinetic parameters (P<0.05). The metabolism of zolpidem tatrate in males was faster than in females. Results indicate that ethnicity has no significant impact on the pharmacokinetics of zolpidem tatrate after a single oral dose in healthy Chinese subjects. However, an effect of gender on the pharmacokinetics of zolpidem tatrate can be noted.

Genetic polymorphisms of drug-metabolizing phase I enzymes CYP3A4, CYP2C9, CYP2C19 and CYP2D6 in Han, Uighur, Hui and Mongolian Chinese populations.

We randomly evaluated 672 unrelated, healthy Chinese volunteers (136 Han, 214 Uighur, 164 Hui and 158 Mongolian) to compare CYP3A4, CYP2C9, CYP2C19 and CYP2D6 allele frequencies. Genomic DNA was extracted from peripheral leukocytes and genotyped for CYP3A4*5, CYP3A4*18, CYP2C9*2, CYP2C9*13, CYP2C19*2, CYP2C19*3 and CYP2D6*10 by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Our results showed that there is no significant difference in the distribution of CYP2C19*3 and CYP3A4*18 genotypes in the Han, Uighur, Hui and Mongolian Chinese populations. The CYP2C9*13/*13 and CYP3A4*5 genotypes were not observed in any of the four Chinese populations. We found a higher incidence of the CYP2C9*2 allele in Uighur populations, compared to the Han, Hui and Mongolian populations. The incidence of the CYP2C19*2 allele in the Han population was not significantly different from that in the Uighur, Hui or Mongolian populations; however, the Uighur population showed significantly lower rates of this allele than the Hui and Mongolian populations, and the Mongolian population had a significantly lower incidence of this allele than the Hui population. There was no significant difference in the presence of the CYP2D6*10 allele in the Mongolian, Han or Hui populations. However, the Uighur population showed significantly lower rates of this allele than the other three populations. These findings provide basic genetic information for further pharmacogenomic investigations in the Chinese population.

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.