Mitoquinone (
MitoQ(10)
mesylate) is a mitochondria-targeted
antioxidant formulated for
oral administration in the treatment of
neurodegenerative diseases. We have investigated the absorption and metabolism of
MitoQ(10) in Caco-2 cell monolayers. The intracellular accumulation of
MitoQ(10) was 18-41% of the total amount of
MitoQ(10) added. Some of the intracellular
MitoQ(10) was reduced to
mitoquinol and subsequently metabolized to
glucuronide and
sulfate conjugates. Transport of
MitoQ(10) was polarized with the apparent permeability (P(app)) from basolateral (BL) to apical (AP) (P(appBL-->AP)) being >2.5-fold the P(app) from apical to basolateral (P(appAP-->BL)). In the presence of 4%
bovine serum albumin on the basolateral side, the P(appAP-->BL) value increased 7-fold compared with control. The P(appBL-->AP) value decreased by 26, 31 and 61% in the presence of
verapamil 100 microM,
ciclosporin 10 and 30 microM, respectively, whereas the P(appAP-->BL) value increased 71% in the presence of
ciclosporin 30 microM. Apical efflux of
mitoquinol sulfate and
mitoquinol glucuronide conjugates was significantly decreased by
ciclosporin 30 microM and the
breast cancer receptor
protein (BCRP) inhibitor,
reserpine 25 microM, respectively. These results suggested that the bioavailability of
MitoQ(10) may be limited by intracellular metabolism and the action of
P-glycoprotein and BCRP. However, the dramatic increase in absorptive P(app) in the presence of
bovine serum albumin on the receiver side suggests these barrier functions may be less significant in-vivo.