| Title | Blood-brain barrier transport of naloxone does not involve P-glycoprotein-mediated efflux. | | Author(s) | Suzuki T, Miyata M, Zaima C, Furuishi T, Fukami T, Kugawa F, Tomono K | | Institution | Department of Pharmaceutics, College of Pharmacy, Nihon University, Chiba, Japan. | | Source | J Pharm Sci 2009 Jun 15. | | Abstract | The blood-brain barrier (BBB) transport of naloxone, a potent and specific opioid antagonist, was investigated in rats using the brain uptake index method and the brain efflux index method. The apparent influx clearance of [(3)H]naloxone across the BBB was 0.305 mL/min/g brain. [(3)H]naloxone was eliminated from the brain with an apparent elimination half-life of 15.1 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [(3)H]naloxone across the BBB was 0.152 mL/min/g brain, which was calculated from the elimination rate constant (4.79 x 10(-2) min(-1)) and the distribution volume in the brain (3.18 mL/g brain). The influx clearance across the BBB was two times greater than the efflux clearance. The elimination of [(3)H]naloxone from the brain was not inhibited in the presence of the typical P-glycoprotein (P-gp) inhibitors such as quinidine, verapamil, vinblastine, and vincristine, indicating that naloxone is not a P-gp substrate in the rat. In vitro experiments by using human multidrug resistance 1 (MDR1)/P-gp overexpressing HeLa cells showed that the uptake of naloxone by the cells did not change in the presence of the P-gp inhibitors. In conclusion, the present results obtained from in vivo and in vitro studies suggest that P-gp is not involved in the BBB transport of naloxone. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19530072 |
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