Affiliation:
1. Inveresk Research International Ltd, Tranent, UK
Abstract
Objective: To investigate the effect of diosmin particle size on the rate and extent of absorption and excretion of total radioactivity, following oral administration of micronized and non-micronized [14C]-diosmin to New Zealand White rabbits. Design: This study was conducted in a 2 x 12 cross-over design at a uniform target dose level of 10 mg/kg, and was conducted according to Good Laboratory Practice. The micronized formulation was prepared using a Microdismembrator II, and all prepared doses were suspended in 0.5% w/v aqueous methylcellulose at a target concentration of 5 mg/ml. Particle size analysis indicated that in the micronized formulation, 90% of particles were ≤2 <m, and in the non-micronized formulation, more than 75% of particles were ≥3 <m. Results: Analysis of percentage dose excreted via urine post-dose indicated a higher urinary output in the animals that received micronized diosmin (mean of 72% dose in both 0–48 h and 0–168 h) compared with means of 16% dose and 17% dose, respectively, in animals that received the non-micronized formulation. Statistical analysis showed these differences to be highly significant ( p < 0.0001), with no evidence of sequence or phase effects. Conclusion: Reduction of particle size of [14C]-diosmin when administered orally as a suspension to rabbits resulted in a marked increase in the proportion of the dose excreted in urine. This increase was considered to reflect an increased absorption of radiolabelled components from the micronized dose.
Subject
Cardiology and Cardiovascular Medicine,General Medicine
Cited by
7 articles.
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