Bioequivalence of Metoprolol Tartrate Tablets in healthy volunteers / 中国临床药理学与治疗学

AIM: To study the bioequivalence of domestic and imported Metoprolol Tartrate Tablets in Chinese healthy volunteers.METHODS: According to the rule published by SFDA,the serum concentration of 20 selected volunteers among 18 to 40 years old was determined by HPLC-fluorescence detection after giving domestic and imported Metoprolol Tartrate Tablets 0.1g,and the pharmacokinetic parameters were calculated by DAS software.RESULTS: The method of HPLC-fluorescence detection to study the pharmakokinetics of Metoprolol Tartrate was sensitive,reliable,accurate and reasonable.The main pharmakokinetics parameters of domestic and imported Metoprolol Tartrate Tablets were T_(max):(1.11)?(0.36 h) and(1.39)?(0.65 h) respectively;C_(max):(269.20)?(87.15)(?g?L~(-1)) and(262.03)?(75.52)(?g?L~(-1)) respectively;AUC_(0-12h):(1088.91)?(510.52)(?g?L~(-1)?h) and(1098.29)?5(55.14)(?g?L~(-1)?h) respectively.The relative bioavailability of domestic Metoprolol Tartrate Tablets was(100.09)%.CONCLUSION: The domestic and imported Metoprolol Tartrate Tablets was bioequivalents.

Comparison of genotype polymorphism of cytochrome CYP2C19 between Chinese Han subjects and Chinese Meng subjects / 中国临床药理学与治疗学

AIM: To compare genotype polymorphism of cytochrome CYP2C19 between Chinese Meng subjects and Chinese Han subjects. METHODS: The genotype polymorphism was analyzed by PCR RFLP (Restriction Fragment Length Polymorphism) in 74 subjects of healthy Chinese Han and 6 subjects of Chinese Meng. RESULTS: Of the 74 genotyped healthy subjects, 31 ( 41.9 %) were homozygous for wildtype (wt/wt), 9 ( 12.2 %) were homozygous for CYP2C19m1 and CYP2C19m2 (m1/m1 or m1/m2 or m2/m2), and 34 ( 45.9 %) were heterozygous for CYP2C19m1 or CYP2C19m2 (m1/wt or m2/wt). Among the 6 genotyped Chinese Meng, 1 ( 16.7 %) was homozygous for wildtype (wt/wt), 2 ( 33.3 %) were homozygous for mutant allele CYP2C19m1 and CYP2C19m2 (m1/m1 or m1/m2 or m2/m2), and 3( 50.0 %) were heterozygous for CYP2C19m1 or CYP2C19m2 (m1/wt or m2/wt); no homozygous genotype for CYP2C19m2(m2/m2)was found in this study. CONCLUSION: There is no statistical difference in occurrence of wt/wt and m1/m1 between in 74 subjects of healthy Chinese Han and 6 subjects of Chinese Meng.

Pharmacokinetic study of bifonazole in human / 中国药学杂志

OBJECTIVE　To study the pharmacokinetics of bifonazole in healthy human,in order to evaluate the safety of bifonazole.METHODS　8 healthy volunteers were given single dose of 300 mg bifonazole solution and cream preparation respectively in a cross-over design.Blood samples were collected at the designed time,and the concentrations of bifonazole in plasma were determined by means of GC-MS(SIM) quantitative method.The pharmacokinetic parameters were calculated with the 3P87 software.RESULTS　The plasma concentration-time curves of the two preparations were fitted to two-compartment open model.The tmax of the solution and cream preparations were 2.91 h and 5.62 h,cmax 713.46 ng.mL-1 and 410.70 ng*mL-1,respectively.The cream preparations absorption,distribution and clearance was a little slower than that of the solution preparation.However,no significant difference in their AUC.CONCLUSION　Bifonazole is a safe drug,and clinical use of the solution and cream preparation in turn is suggested to improve its therapeutic efficacy.

Cytochrome P450 and genetic polymorphism / 中国药理学通报

Cytochrome P450 enzyme are an important enzyme family in drug metabolism. Human cytochrome P450 enzymes have been studied entensively about their polymorphism in recent years. polymorphism of CYP2C19 and CYP2D6 have been detected at both phenotypic and genotypic level, and their molecular mechanism have been studied entensively, however, the molecular mechanism of other enzymes for exzample CYP2C9,CYP1A1,CYP2E1 et al) is being discussed, though these enzymes possiblely exist polymorphism. The article summarizes the substrates of P450, molucular mechanism of polymorphism, and paticular reference to the effects of this variation on drug metabolism and susceptibility to chemically-induced diseases.

The plasma concentration of omeprazole and metabolites 5′-hydroxy omeprazole, omeprazole sulphone are determinated by HPLC / 中国药理学通报

AIM To set up a method which can determining the blood concentration of omeprazole and its metabolite 5′ omeprazole, omerpazole sulphone in order to study its cinical pharmacokinetics. METHODS The blood concentration of omerpazole was determinated by HPLC. RESULTS Calibrated standard curve of omeprazole in blood is Y=-0 004 499+0 001 909X (r =0 9990), the recoveries of three concentrations 50, 500, 2 000 mg?L -1 are 90 36, 109 62, 108 91%, respectively; and the precisions are 9 86,7 86, 15 52% , respectively. Calibrated standard curve of its metabolite 5′ OH omeprazole in plasma is Y=-0 003 659+0 001 328X(r =0 9970), the recoveries of three concentrations 20, 200, 1 000 mg?L -1 are 79 42%, 96 49%, 95 04%, respectively; and the precisions are 8 95%, 4 52%, 9 73%, respectively. Calibrated standard curve of its another metabolite omeprazole sulphone in plasma is Y=0 009 248+0 001 765X (r =0 999 2), the recoveries of three concentrations 20, 200, 1 000 mg?L -1 are 94 44%, 105 59%, 104 26%, respectively; and the precisions are 8 72, 8 58, 9 60%, respectively. After 20 mg omeprazole were administered by a voluteer via oral, C max of 5′ OH omeprazole, omeprazole, and omerpazole sulphone were 14 622 7, 408 433 2, 454 363 7 mg?L -1 . CONCLUSION The method is good enough to study pharmacokinetics of omeprazole.