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KMID : 0043319990220020165
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Archives of Pharmacal Research
1999 Volume.22 No. 2 p.165 ~ p.172
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Permeability of a Capsaicin Derivative, [14C]DA-5018 to Blood-Brain Barrier Corrected with HPLC Method
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Kang Young-Sook
Kim Jong-Mi
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Abstract
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In the present work , the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker, and , indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of agreed with those reported (percentage injected dose minute per milliliter (%IDmin/ml) and , respectively). Elimination half-life and AUC of is corrected by the PHLC analysis, 19.61.2 min and 7.690.85% IDmin/ml, respectively. The metabolic rate of was very rapid. The blood-brain barrier permeability surface area (PS) product of was calculated to be 0.240.05 l/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.
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KEYWORD
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Blood-brain barrier, Capsaincin, DA-5018, Vanilloid receptor
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