Comparison of the absorption of micronized (Daflon 500® mg) and nonmicronized 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting

✍ Scribed by R. C. Garner; J. V. Garner; S. Gregory; M. Whattam; A. Calam; D. Leong

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 155 KB
• Volume: 91
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1168

✦ Synopsis

Da¯on 500 1 mg, is a micronized puri®ed ¯avonoid fraction, containing 90% w/w diosmin and 10% w/w of ¯avonoids expressed as hesperidin, used clinically in the treatment of chronic venous insuf®ciency and hemorrhoidal disease. This study was designed to investigate the in¯uence of particle size on the overall absorption of diosmin after oral administration of micronized (mean particle size 1.79 mm, with 80% of particles having a size lower than 3.45 mm) and nonmicronized diosmin (mean particle size 36.5 mm, with 80% of particles comprised between 19.9 and 159 mm). 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 signi®cantly improved with the micronized (57.9 AE 20.2%) compared with the nonmicronized material (32.7 AE 18.8%). Statistical comparison of the urinary excretion of the two pharmaceutical formulations showed this difference to be highly signi®cant (p 0.0004, analysis of variance). The overall excretion of the radiolabeled dose was 100% with mean AE SD of 109 AE 23% and 113 AE 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 ef®cacy 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.