quantitative in vitro and in vivo evaluation of intestinal and blood-brain barrier transport kinetics of the plant n-alkylamide pellitorine
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ID: 206964
2016
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Abstract
Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS2 method was used to quantify pellitorine. Results. Pellitorine was able to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the basolateral-to-apical side with apparent permeability coefficients between 0.6·10-5 and 4.8·10-5 cm/h and between 0.3·10-5 and 5.8·10-5 cm/h, respectively. In rats, a serum elimination rate constant of 0.3 h−1 was obtained. Intravenous injection of pellitorine in mice resulted in a rapid and high permeation of pellitorine through the BBB with a unidirectional influx rate constant of 153 μL/(g·min). In particular, 97% of pellitorine reached the brain tissue, while only 3% remained in the brain capillaries. An efflux transfer constant of 0.05 min−1 was obtained. Conclusion. Pellitorine shows a good gut permeation and rapidly permeates the BBB once in the blood, indicating a possible role in the treatment of central nervous system diseases.
| Reference Key |
veryser2016biomedquantitative
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| Authors | ;Lieselotte Veryser;Nathalie Bracke;Evelien Wynendaele;Tanmayee Joshi;Pratima Tatke;Lien Taevernier;Bart De Spiegeleer |
| Journal | spectrochimica acta - part a: molecular and biomolecular spectroscopy |
| Year | 2016 |
| DOI |
10.1155/2016/5497402
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| URL | |
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