Oral Bioavailability of Sesamol in Rats
Date Issued
2005
Date
2005
Author(s)
Hsieh, Hsin-Ling
DOI
zh-TW
Abstract
Sesamol (benzo[1,3]dioxol-5-ol) has been generally regarded as the main antioxidative component in sesame oil. It was produced from sesamolin during the bleaching process of sesame oil with acid clay or upon roasting of sesame seed. The purpose of this study was to investigate the oral bioavailability and pharmacokinetic characteristics of sesamol in rats, both microdialysis and traditional blood sampling methods were employed. We developed a rapid and sensitive high performance liquid chromatographic method coupled with microdialysis system to measure the unbound sesamol from various biological fluids. Multiple microdialysis probes were concurrently inserted into the jugular vein, bile duct, brain striatum and the median lobe of liver of each anesthetized rat for sampling after sesamol administration (30 mg/kg) through the femoral vein. Separation of the unbound sesamol from various biological fluids was performed by a reversed phase C18 column (4.6 mm i.d. × 250 mm, 4 μm particle size). The mobile phase consisted of acetonitrile-10 mM sodium dihydrogen phosphate buffer (35:65, v/v) (adjusted to pH 4.0 with phosphoric acid) at a flow rate of 1 ml/min. The UV detector wavelength was set at 294 nm. The results showed that the maximum concentration of sesamol in blood, bile, brain and liver were 8.36 ± 1.47, 2.65 ± 0.63, 3.33 ± 0.55 and 1.17 ± 0.14 μg/ml; the half-lives were 7.51 ± 1.01, 10.3 ± 4.0, 6.49 ± 2.18 and 6.49 ± 1.14 min; the area under the concentration versus time curves (AUCs) were 75.3 ± 18.2, 44.1 ± 8.3, 44.0 ± 7.0 and 11.4 ± 7.6 min μg/ml, respectively. The extent of systemic unbound sesamol distributed to bile, brain and liver, calculated as AUCbile/AUCblood, AUCbrain/AUCblood and AUCliver/AUCblood were 0.602 ± 0.126, 0.603 ± 0.120 and 0.140 ± 0.074. In addition, the results indicated that sesamol penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion. The oral bioavailability is defined as the fraction of the dose which reaches the systemic circulation as intact drug. Blood samples were collected at various time intervals after sesamol administration and then assayed by a validated HPLC system. The separation of sesamol in rat plasma was performed under the similar HPLC condition as in the microdialysis samples except the mobile phase was adjusted to pH 4.15. After sesamol administration (30, 100 and 300 mg/kg, p.o. and 30 mg/kg, i.v.), the maximum concentration of sesamol were 11.2 ± 6.2, 22.2 ± 7.3, 60.5 ± 14.0 and 38.8 ± 16.8 μg/ml; the half-lives were 9.43 ± 4.33, 13.2 ± 4.9, 11.1 ± 2.4 and 15.3 ± 5.8 min; AUCs were 110 ± 70, 443 ± 150, 1140 ± 360 and 343 ± 96 min μg/ml, respectively. The results showed that the concentrations of sesamol declined rapidly and the elimination half-lives did not relate to the dosage ranges. AUCs presented dose dependent manner. These results suggested that sesamol appears a linear pharmacokinetic phenomenon. The oral bioavailability of sesamol was 34.8% in rats. The protein binding ratio of sesamol was 82.8% in rat plasma.
Subjects
芝麻酚
口服生物可利用率
sesamol
oral bioavailability
Type
thesis
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