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Study on the Pharmacokinetics of Midazolam Tablet in Chinese Healthy Volunteers of Different Ethnic Groups

Author: MaoGuiFu
Tutor: GuoTao；XiaDongYa
School: Shenyang Pharmaceutical University
Course: Clinical Pharmacy
Keywords: Midazolam Pharmacokinetic Population pharmacokinetics HPLC Han Mongolian Uighur Hui Korean
CLC: R96
Type: Master's thesis
Year: 2009
Downloads: 35
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Abstract

Objective: To study the pharmacokinetics Chinese Han, Mongolian, Uygur, Hui and Korean healthy subjects, a single dose of oral midazolam film, ethnic, gender and other factors midazolam tablet pharmacokinetics learn the impact to provide a scientific basis for the war wounded to medical treatment and clinical use of drugs. Methods: Chinese Han, Mongolian, Uygur, Hui and Korean healthy subjects, 10 (male and females), a single oral dose of midazolam tablets 15 mg, respectively medication before and after taking the point-in-time venous blood. HPLC-UV method for the determination of midazolam midazolam plasma concentrations, and non-compartment model to estimate the pharmacokinetic parameters use DAS2.0 program. Using statistical software SPSS13.0 program pharmacokinetic parameters of different ethnic subjects analysis of variance or KrusKal-Wallis rank sum test, to determine whether the ethnic and gender factors on the pharmacokinetics of midazolam tablets significantly impact on the pharmacokinetic parameters of multiple comparisons between the national application of the Student-Newman-Keuls test or the Mann-Whitney test test further determine differences exist between nations which; using NONMEM program of midazolam plasma concentration time data and ethnicity, gender, age and other factors affecting the population analysis. Results: RP-HPLC method for the linear range of 2.5-320 ng · mL-1, the minimum detectable concentration of 2.5 ng · mL-1, the recoveries of 100.2% -105.1%, days, daytime RSD ≤ 15% (n = 5), the indicators are in line with the provisions of the relevant national clinical biological sample analysis method. Chinese Han, Mongolian, Uygur, Hui and Korean healthy subjects, a single dose of oral midazolam piece pharmacokinetic parameters were: Cmax (103.1 ± 26.4), (74.9 ± 33.7), (124.8 ± 50.0), (130.0 ± 38.3) (189.0 ± 82.1) ng · mL-1; Tmax (1.52 ± 0.75), (1.03 ± 0.65), (0.78 ± 0.54), (0.99 ± 0.87) and (0.63 ± 0.72) h; AUC0-12 (368.9 ± 103.6), (260.4 ± 137.8), (343.2 ± 150.9), (397.2 ± 99.8) (369.8 ± 85.5) ng · h · mL-1; AUC0-∞ (397.3 ± 124.1) , (275.1 ± 146.2), (360.9 ± 163.4), (428.0 ± 92.3) and (403.3 ± 124.3) ng · h · mL-1; CLz / F (41.0 ± 12.3) (89.2 ± 88), (50.6 ± 26.4), (36.8 ± 9.2) and (39.7 ± 9.5) L · h-1; Vz / F (170 ± 51), (247.3 ± 191) (123.8 ± 37.3) (191.7 ± 133) and (204.4 ± 96.7) L the; t1/2z (2.96 ± 0.77), (2.22 ± 0.73), (1.93 ± 0.70), (3.48 ± 1.92) and (3.82 ± 2.33) h; MRT0-12h (3.61 ± 0.42), (2.89 ± 0.49), (2.78 ± 0.80), (3.40 ± 0.22) and (2.97 ± 0.48) h. Cmax variance analysis of five ethnic groups, the results show that the Mongolian Cmax lower than the remaining four races, the significant difference was statistically significant (P lt; 0.05); Korean in Cmax than the remaining four races, but only with the Han, Mongolian significant difference statistically significant (P lt; 0.05). Mongolian Cmax and the remaining four ethnic Korean in Cmax weight-adjusted with remaining four ethnic differences have significant sexual statistical significance (P lt; 0.05). Groups of rank-test results show that the midazolam piece of the the pharmacokinetic parameters MRT0-of 12h, t1/2z and Tmax ethnic differences with significant statistical significance (P lt; 0.05), while the parameter AUC0-12h, AUC0 - ∞, CLZ / F and VZ / F ethnic differences were not significant statistically significant (P gt; 0.05). The impact of gender on all pharmacokinetic parameters was no significant statistical significance (P gt; 0.05). Respectively the 12h of the pharmacokinetic parameters MRT0-five ethnic groups, t1/2Z and Tmax for multiple comparisons, the results showed that: of Han and Hui MRT0-12h than Mongolian, Uygur, Korean long, and there was significant statistical significance (P lt; 0.05) MRT0-12h difference in other peoples statistically significant (P gt; 0.05); the Han significantly longer than Tmax Uygur, Korean of Tmax (P lt; 0.05) , Tmax among other ethnic groups showed no significant difference (P gt; 0.05); the Uygur t1/2Z than Hui and Korean short the Mongolian t1/2Z shorter than Korean, and these differences have significant statistically significant (P lt; 0.05), tl / 2 among the other ethnic groups showed no significant statistical significance (P gt; 0.05); Mongolian CLz / F large than other ethnic groups, but no significant statistical significance (P gt; 0.05). Midazolam piece population pharmacokinetic studies have shown that ethnic factors have a significant impact for the clearance and the apparent volume of distribution, particularly evident Mongolian pharmacokinetics; renal function (blood urea nitrogen factors) clearance have a significant impact; significant influence of the age factor in the apparent volume of distribution. Gender on the clearance rate, apparent distribution volume is negligible. The main pharmacokinetic parameters AUC0-12h, Cmax, CLZ / F and t1/2Z for of the biggest differences between the different ethnic individual were 15,20,14, and more than nine times, with the biggest difference between the multiples of the national inter-individual 12 8,11 and 4, indicating that individual differences in midazolam pharmacokinetics of alprazolam tablets. After a single oral dose of 15 mg midazolam tablets, Han, Mongolian, Uygur, Hui and Korean total of 27 patients (13 males, 14 females) healthy subjects drug - curve obvious bimodal phenomenon. Conclusion: The pharmacokinetics of midazolam tablets differences between Chinese Han, Mongolian, Uygur, Hui and Korean were considered statistically significant; renal function (blood urea nitrogen factors) clearance rate significantly impact; Age on the apparent volume of distribution significantly influence; gender on the pharmacokinetics of midazolam no significant impact. More than half of the subjects of the drug - curve bimodal phenomenon. Main pharmacokinetic parameters of individual differences in the clinical application of midazolam films should pay attention to adjust the dose.

Study on the Pharmacokinetics of Midazolam Tablet in Chinese Healthy Volunteers of Different Ethnic Groups

Abstract

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