In vivo evidence for the efflux transport of pentazocine from the brain across the blood–brain barrier using the brain efflux index method

Abstract

The efflux transport of pentazocine (PTZ) from the brain across the blood–brain barrier (BBB) was investigated using the Brain Efflux Index method. PTZ was eliminated with the apparent elimination half-life of 13.0 min after microinjection into the parietal cortex area 2 region of the rat brain. The apparent efflux clearance of PTZ across the BBB was 137 μl/min/g brain, which was calculated from the elimination rate constant (5.35 × 10⁻² min⁻¹) and the distribution volume in the brain (2.56 ml/g brain). The efflux transport of PTZ was decreased in the presence of unlabeled PTZ, suggesting that PTZ is eliminated by a carrier-mediated transport system across the BBB. To characterize the efflux transport of PTZ from the brain in vivo, the effects of several compounds on the efflux transport of PTZ were investigated. P-glycoprotein (P-gp) inhibitors (verapamil and quinidine) reduced the PTZ efflux transport. In addition, the efflux transport of PTZ was inhibited by organic cations such as _l-carnitine and tetraethylammonium (TEA), whereas organic anions such as p-aminohippuric acid, probenecid and taurocholate did not affect the PTZ efflux transport. The present results suggest that PTZ is transported from the brain across the BBB via _l-carnitine/TEA-sensitive carrier-mediated efflux transport system(s) in addition to P-gp.

Keywords::

• Pentazocine
• blood–brain barrier
• Brain Efflux Index method
• p-glycoprotein