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.