Garner R C, Garner J V, Gregory S, Whattam M, Calam A, Leong D
The Centre for Biomedical Accelerator Mass Spectrometry (CBAMS Ltd.) Sand Hutton, York Y041 ILZ, United Kingdom.
J Pharm Sci. 2002 Jan;91(1):32-40. doi: 10.1002/jps.1168.
Daflon 500 mg, is a micronized purified flavonoid fraction, containing 90% w/w diosmin and 10% w/w of flavonoids expressed as hesperidin, used clinically in the treatment of chronic venous insufficiency and hemorrhoidal disease. This study was designed to investigate the influence of particle size on the overall absorption of diosmin after oral administration of micronized (mean particle size = 1.79 microm, with 80% of particles having a size lower than 3.45 microm) and nonmicronized diosmin (mean particle size = 36.5 microm, with 80% of particles comprised between 19.9 and 159 microm). In a double blinded, cross-over study design, 500 mg tablets containing trace amounts (approximately 25 nCi) of (14)C-diosmin were administered to 12 healthy male volunteers as a single oral dose. Accelerator mass spectrometry and liquid scintillation counting were used for the measurement of (14)C-diosmin in urine and feces. Absorption of (14)C-diosmin from the gastrointestinal tract, measured by the urinary excretion of total radioactivity, was significantly improved with the micronized (57.9 +/- 20.2%) compared with the nonmicronized material (32.7 +/- 18.8%). Statistical comparison of the urinary excretion of the two pharmaceutical formulations showed this difference to be highly significant (p = 0.0004, analysis of variance). The overall excretion of the radiolabeled dose was 100% with mean +/- SD of 109 +/- 23% and 113 +/- 20% for the micronized and nonmicronized forms, respectively. The results of this study show: 1. the impact of a reduction of particle size on the extent of absorption of diosmin, giving a pharmacokinetic explanation to the better clinical efficacy observed with the micronized formulation, and 2. the use of accelerator mass spectrometry in conjunction with liquid scintillation counting in measurement of bioavailability in a human cross-over study comparing two drug formulations containing trace amounts of radioactivity.
爱脉朗500毫克，是一种微粉化的纯化黄酮类成分，含有90%（重量/重量）的地奥司明和10%（重量/重量）以橙皮苷表示的黄酮类化合物，临床上用于治疗慢性静脉功能不全和痔疮疾病。本研究旨在探讨粒径对口服微粉化（平均粒径 = 1.79微米，80%的颗粒粒径小于3.45微米）和非微粉化地奥司明（平均粒径 = 36.5微米，80%的颗粒粒径在19.9至159微米之间）后地奥司明总体吸收的影响。在一项双盲、交叉研究设计中，向12名健康男性志愿者单次口服给予含有微量（约25纳居里）(14)C - 地奥司明的500毫克片剂。采用加速器质谱法和液体闪烁计数法测量尿液和粪便中的(14)C - 地奥司明。通过总放射性的尿排泄量来衡量，胃肠道对(14)C - 地奥司明的吸收，微粉化制剂（57.9 +/- 20.2%）相比于非微粉化制剂（32.7 +/- 18.8%）有显著改善。两种药物制剂尿排泄量的统计学比较显示这种差异具有高度显著性（p = 0.0004，方差分析）。放射性标记剂量的总体排泄率为100%，微粉化和非微粉化形式的平均排泄率分别为109 +/- 23%和113 +/- 20%。本研究结果表明：1. 粒径减小对地奥司明吸收程度的影响，为微粉化制剂观察到的更好临床疗效提供了药代动力学解释；2. 在比较两种含有微量放射性的药物制剂的人体交叉研究中，加速器质谱法与液体闪烁计数法联合用于生物利用度测量。
