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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.
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BACKGROUND:Whether determination of tacrolimus blood concentration by different immunoassay methods can influence predictive ability to immunosuppressive effects and toxicity, and whether it can be more sensitive to reflect blood concentration in patients with renal dysfunction are worthy of studying. OBJECTIVE:To analyze the correlation of tacrolimus (FK506) concentrations determined by enzyme-multiplied immunoassay technique (EMIT) and enzyme linked immunosorbent assay (ELISA) in combination with renal function parameters. METHODS:133 clinical blood samples were col ected. EMIT and ELISA techniques were used to determine the FK506 concentration. The correlation of two determination methods were analyzed, combined with renal function. RESULTS AND CONCLUSION:In patients with renal dysfunction, the mean results and standard deviation mensurated by ELISA were higher than those by EMIT. For blood concentration in 5-20μg/L by ELISA, the incidence of renal dysfunction occurred less than by EMIT. The overal mean results of blood concentration for two methods appeared no significant difference (r=0.904 5, P>0.05). When the concentration was less than 2.0μg/L, the concentration results by EMIT were higher than those by ELISA (P0.05). These findings indicate that EMIT and ELISA has good correlation, which are both suitable for clinical routine determination of plasma concentration. It is not recommended for applying EMIT method to determine low blood concentrations (<2.0μg/L). The reference range of concentration should be compartmentalized depending on combination of determination methods and renal function.
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Aim To investigate and compare the phar-macokinetics of doxapram injection in healthy subjects of different Chinese nationalities including Han, Mon-golian, Korean, Hui and Uigur, and the influence of gender,in order to provide instruction and help for the usage of doxapram for both clinic and remedy of battle wound. Methods An HPLC-UV method was used to determine the plasma concentration of doxapram. Fifty healthy subjects ( five males and five females of each nationality) were recruited for the study. A single dose of 50 mg doxapram was administered intravenously to the healthy subjects, and blood samples were collected at various predetermined time points. The pharmacoki-netic parameters were calculated by DAS software and were compared by SPSS 13. 0 software, in order to as-sess the influence of nationality or gender on pharmaco-kinetics of doxapram. Results The results indicated that the pharmacokinetic profile of doxapram in vivo could be described as two-compartment model. The main pharmacokinetic parameters for Han, Mongolian, Korean, Hui and Uygur were as follows: Cl ( 0. 25 ± 0. 11 ) , ( 0. 33 ± 0. 11 ) , ( 0. 27 ± 0. 07 ) , ( 0. 26 ± 0. 06) and (0. 39 ± 0. 25) L·h-1 ·kg-1 , while Cmax (1. 55 ± 0. 52 ) , ( 1. 02 ± 0. 30 ) , ( 1. 31 ± 0. 47 ) , (1. 48 ± 0. 46 ) and ( 0. 99 ± 0. 35 ) mg · L-1 . The AUC0-12. 5 , AUC0-∞ and Cmax of Chinese Han were sig-nificantly higher than those of Uigur and Mongolian ( P0. 05 ) . There were statistically significant differences in Vc , Vd and CL between young males and females ( P < 0. 05 ) . Conclusion The large inter-individual variation in the main pharmacoki-netics suggests the dosage of doxapram should be ad-justed for different nationalities for both clinic and rem-edy of battle wound.
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Aim To study the pharmacokinetics of midazolam tablet after a single oral dose in Hui,Koreanand Han healthy volunteers.Methods Ten Hui, ten Han and nine Korean healthy volunteers were involved in the study. Each subject received a single dose of 15 mg midazolam tablets. The plasma concentration was determined by HPLC. The pharmacokinetic parameters were calculated by DAS2.0 software and compared by one-way analysis of variance or KrusKal-Wallis rank test for PK parameters of different nationalities.Results There were statistically significant differences between Hui,Korean and Han nationality for PK parameters C_(max),MRT_(0～12 h) and T_(max)(P＜0.05).The ranges of interindividual variation in the different ethnic groups and the same ethnic group were large.There were not satisfactory differences between young males and females for all pharmacokinetic parameters(P＞0.05).Followimg oral administration, doublepeaks in midazolam blood concentration-time profiles were observed in more than half of subjects.Conclusion There are large interindividual variation and statistically significant difference in pharmacokinetics of midazolam tablet between Chinese Hui, Korean and Han.These observations suggest the dosage of midazolam should be adjusted in clinical practice.
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OBJECTIVE: To establish RP-HPLC method for the determination of fluconazole in human plasma.METHODS: After liquid-liquid extraction,the plasma sample was analyzed on Diamonsil C18 column with column temperature set at room temperature.The mobile phrase consisted of methanol-0.07% aqueous solution of triethylamine(50∶ 50) with a flow rate of 1mL? min-1.The UV detection wavelength was set at 210nm,and phenacetin was used as the internal standard.RESULTS: The linear range of fluconazole was 0.15～ 10.0mg? L-1(r=0.999 2),with lower quantification limit at 0.15mg? L-1.The intra-day RSD was between 3.37% and 7.48% and the inter-day RSD was between 7.03% and 12.05%;the method recovery was 103.64%(RSD=5.04%),and the average extraction recovery was between 83.81%(RSD=5.77%).CONCLUSION: This method was sensitive,accurate,rapid and reproducible,and suitable for the content determination of fluconazole in plasma.
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AIM: To monitor the concentration of tacrolimus in whole blood in liver transplant recipients and establish an optimal therapeutic window of tacrolimus, in order to provide information for rational usage in clinic. METHODS: The whole blood concentrations of tacrolimus were measured by ELISA. The levels of tacrolimus in 1190 samples from 138 liver transplant recipients were compared and studied. RESULTS: The whole blood concentration of tacrolimus is gradually decreased with time after operation. The optimal therapeutic window of tacrolimus for liver transplant recipients was 8-15 ?g?L -1 within 1 month after operation, 6-12 ?g?L -1 from the 2nd to 3rd months, 5-10 ?g?L -1 from the 4th to 6th months and 3-8 ?g?L -1 after 6 months, respectively. CONCLUSION: It is necessary to routinely monitor blood concentration of tacrolimus. The satisfying therapeutic effects will be obtained if dosage regimens will be individualized according to optimal therapeutic window.
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Object To develop an HPLC method for the determination of plasma level of ferulic acid and study the in vivo pharmacokinetics in rats. Methods The used analytical column was Nucleosil C_ 18 . The mobile phase was methanol-water-acetic acid (35∶65∶0.1). The flow rate was 1.0 mL/min and detection wavelength at 320 nm. Plasma samples were prepared for analysis by addition of internal standard (Tinidazole) followed by extracting with ethyl acetate. Results Linear caliration curve was obtained by plotting concentration vs peak area ratio over the rang 0.25—16.0 mg/L with a correlation coefficient of 0.999 2. The average recovery of ferulic acid was 96.9%—100.6%. The minimum detectable concentration of ferulic acid was 0.2 mg/L. The relative standard deviations for within-day and between-days were less than 3.0% and 5.3%,respectively. The plasma concentration-time curve of ferulic acid in Xinshu Oral Liquid ig given to rats was found to fit a two-compartments model with T_ 1/2? of 12.6 min and T_ 1/2? of 305 min. Conclusion The method is simple,rapid,accurate,and precise, which can be used for the determination of plasma level of ferulic acid and the study of its pharmacokinetics.
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OBJECTIVE: To investigate the pharmacokinetics of zolpidem tartrate tablet in Han healthy volunteers. METHODS: 10 Han health volunteers were given 10 mg zolpidem tartrate tablet via p.o. The plasma concentrations were determined by HPLC-fluorescence method and the pharmacokinetic parameters were calculated by DAS 2.0.1 software. RESULTS: The plasma concentration-time curve of zolpidem tartrate is fitted to one-compartment model with a first order absorption. The main pharmacokinetic parameters were as follows: tmax(0.9?0.5)h,Cmax(190.8?70.6)?g?L-1, t1/2(2.2?0.6)h,Vd/F(0.938?0.256)L?kg-1, CL/F (18.09?10.22)L?h-1, AUC0～12(624.9?190.8) ?g?h?L-1, AUC0～∞(650.1?208.4)?g?h?L-1. CONCLUSION: The pharmacokinetic parameters of zolpidem tartrate in healthy volunlteers are concordant with that stated in literature reports, which can be the basis of pharmacokinetic study in people of different nationalities.
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OBJECTIVE:To provide basis for rational use of verapamil in clinical practice.METHODS:53 patients with hypertension received oral verapamil.The concentrations of verapamil in plasma were determined by fluorespectrophotometry.The population pharmacokinetic parameters were estimated by iterative two stage method and compared with the results estimated by traditional standard two stage method.RESULTS:The population pharmacokinetic parameters in 53 patients were,CL(189.3?59.3)ml/(h?kg),Vd(1.420?0.231)L/kg,T1/2(5.74?190)h,the parameters had no significant difference as compared with the parameters estimated by traditional standard two stage method.CONCLUSION:Iterative two stage method is suitable for estimating population pharmacokinetic parameters,forecasting plasma concentration and optimizing individualized dosage regimen.