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The involvement of P-glycoprotein (P-gp) in pentazocine (PTZ) transport at the blood-brain barrier (BBB) in rats was evaluated by means of an in vivo study using the brain uptake index (BUI) method. The amount of radioactivity in the brain was estimated at different intervals (up to 240 s) after carotid injection in rats. The apparent elimination rate constant (k(test)) due to efflux of PTZ from the brain was calculated as 0.22 min(-1). The observed BUI values of [(3)H]-PTZ (0.35 microM) were not significantly different between 5 and 15 s after the carotid injection. The concentration-dependent uptake of PTZ by the brain was increased gradually by increasing the concentration (0.01-1 mM) of PTZ in the injection solution. The apparent uptake of PTZ by the brain increased in the presence of P-gp inhibitors such as cyclosporin A, quinidine, verapamil and vinblastine after the carotid injection. These results suggest that the increment of PTZ uptake by the brain could be explained by the saturable efflux transport system involving a P-gp-mediated efflux mechanism of PTZ transport at the BBB.

Involvement of P-glycoprotein in Blood-Brain Barrier Transport of Pentazocine in Rats Using Brain Uptake Index Method