OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology

OBJECTIVE: To determine the pharmacokinetics of erythromycin stinoprate capsules and to provide guidance for clinical research. METHODS: Thirty healthy volunteers (15 men and 15 women) were divided into 3 groups randomly, each including 5 men and 5 women. Single oral doses of 250, 500 and 750 mg were given to each volunteer. The concentrations of erythromycin propionate and erythromycin base in the plasma were determined by HPLC-MS. RESULTS All 30 volunteers completed the experiment without adverse reactions. Using 3P87 we analyzed the model and calculated the pharmacokinetic parameters. Three dose groups taking high, middle and low dose were all single compartment model. The pharmacokinetic parameters of erythromycin propionate after taking erythromycin stinoprate capsules were as follows: Low dose group: Ka (2.007 +/- 1.281 )/h, tmax ( actual value) (1.9 +/- 0.6) h, Cmax (437.0 +/- 295.0) microg/L, AUC0-14 (trapezoid area) (1840.2 +/- 1476.87) microg x h/L, Ke (0.329 +/- 0.119)/h, T1/2 (2.45 +/- 0.9) h. Middle dose group: Ka (1.451 +/- 0.380)/h, tmax (1.7 +/- 0.3) h, Cmax (923.1 +/- 217.5) microg/L, AUC0-14 (4542.44 +/- 1579.4) microg x h/L,Ke (0.237 +/- 0.057)/h, T1/2 (3.1 +/- 1.1) h; High dose group: Ka (2.076 +/- 1.559)/h, tmax (1.7 +/- 0.3) h, Cmax (1336.5 +/- 366.0) microg/L, AUC0-14 (7481.5 +/- 2496.2) microg x h/L, Ke (0.266 +/- 0.051)/h, T1/2 (2.7 +/- 0.5) h. The pharmacokinetic parameters of erythromycin were as follows: Low dose group: Ka (1.410 +/- 0.626)/h, tmax (1.8 +/- 0.5) h, Cmax (197.5 +/- 227.6) microLg/L, AUC0-14 (766.4 +/- 981.0) microg x h/L, Ke (0.519 +/- 0.240)/ h, T1/2 (1.6 +/- 0.8) h. Middle dose group: Ka (1.900 +/- 1.049)/h, tmax (1.6 +/- 0.2) h,Cmax (488.3 +/- 216.7) microg/L, AUC0-14( 488.3 +/- 216.7) microg/L, Ke (0.329 +/- 0.057)/h, T1/2(2.2 +/- 0.4) h; High dose group: Ka (1.934 +/- 0.794)/h, tmax (1.7 +/- 0.3) h, Cmax (749.3 +/- 387.2) microg/L, AUC0-14(3820.1 +/- 1966.4) microg x h/L, Ke (0.373 +/- 0.174)/h, T1/2( 2.2 +/- 0.7) h. AUC of both erythromycin propionate and erythromycin base was linearly correlated to the doses; T1/2 was not correlated to the doses, so they followed the first order processes. The pharmacokinetic parameters of erythromycin The erythromycin stinoprate propionate and erythromycin base had no gender differences. Conclusion was absorbed as erythromycin propionate. Cmax reached at about 1.6 h. T1/2 of elimination was 2.4-3.1 h. The active component of erythromycin propionate was erythromycin. Cmax of erythromycin is 1.8, T1/2 is 2.4-3.1 h. In the range of oral dose of 250 to 750 mg, both erythromycin propionate and erythromycin base accorded the first order processes. The pharmacokinetic parameters were different with those reported in foreign documents while the gender difference did not exist in Chinese adults.
Adult ; Area Under Curve ; Biological Availability ; Capsules ; Chromatography, High Pressure Liquid ; methods ; Erythromycin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Female ; Humans ; Male

Objective To evaluate the effect of cytochrome P450 2 D6*10 ( CYP2 D6*10 ) polymorphism on the pharmacokinetics of oral nebivolol after single and multiple doses. Methods Fifteen healthy volunteers which were selected according to their CYP2D6*10 genotype, consisted of 8 of CYP2D6*1 carriers and 7 of CYP2D6*10/*10 geno-types.All subjects received a single dose of 5 mg and multiple doses (5 mg? d-1 , qd, for 7 days) .Nebivolol in plasma were measured by LC-MS/MS.The main pharmacokinetic parameters were calculated by WinNonlin program.Results The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after a single dose were as follows: t1/2 were (9.88 ±5.47), ( 12.29 ±6.19 ) h, AUCinf were ( 7.26 ±5.88 ), (8.56 ±5.20)μg? L-1? h, Cmax were (1.11 ±0.53), (1.42 ±0.75)μg? L-1 , respectively.The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after multiple doses were as follows:t1/2 were (8.56 ±2.38), (7.67 ±4.75) h, AUCinf were (10.62 ±5.62), (12.74 ±7.40)μg? L-1? h, Cmax were (2.05 ±0.83), (2.02 ±0.75)μg? L-1, respectively.No significant differences in the pharmacokinetic parameters of nebivolol were found between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes.The clearance of the multiple doses was significantly lower compared with that of single dose in the different genotyped groups.Conclusion CYP2D6*10 polymorphism has no significant effect on the pharmacokinetics of oral nebivolol after single and multiple doses.The elimination of nebivolol decreases after the multiple doses, which is not affected by CYP2D6*10 polymorphism.

It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.