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The role of active transport in the transcellular movement of the peripheral α 2 -adrenoceptor antagonist, MK-467: An in vitro pilot study.
Canadian Journal of Veterinary Research 2017 October
MK-467 is a peripherally acting α2 -adrenoceptor antagonist due to its low lipid solubility and poor penetration of the blood-brain barrier (BBB). The aim of this study was to assess whether MK-467 could be a substrate of an active efflux transport mechanism. Using Madin-Darby Canine Kidney cells (MDCKII) and MDCKII cells transfected with the human multidrug resistance gene 1, drug transport was assessed in apical-basolateral and basolateral-apical directions. MK-467 was studied at 2 concentrations: 200 and 1000 ng/mL. Samples for analysis were taken at 15, 30, 45, 60, and 90 min after drug application. Drug concentrations were measured using liquid chromatography and mass spectrometry. MK-467 showed no apparent permeability in the apical-basolateral direction, transport in the basolateral-apical direction occurred in both cell lines. Efflux ratios were not calculated. However, MK-467 appeared to undergo active cellular transport. The identity of the transporter requires further investigation.
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