A1 Refereed original research article in a scientific journal
The role of active transport in the transcellular movement of the peripheral α2-adrenoceptor antagonist, MK-467: An in vitro pilot study
Authors: Bennett R., Palviainen M., Peltoniemi M., Vuorilehto L., Scheinin M., Raekallio M., Vainio O.
Publisher: Canadian Veterinary Medical Association
Publication year: 2017
Journal:Canadian Journal of Veterinary Research
Journal name in sourceCanadian Journal of Veterinary Research
Volume: 81
Issue: 4
First page : 318
Last page: 320
ISSN: 19289022 08309000
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.
