P-glycoprotein mediates brain-to-blood efflux transport of buprenorphine across the blood-brain barrier.
The involvement of P-glycoprotein (P-gp) in buprenorphine (BNP) transport at the blood-brain barrier (BBB) in rats was investigated in vivo by means of both the brain uptake index technique and the brain efflux index technique. P-gp inhibitors, such as cyclosporin A, quinidine and verapamil, enhanced the apparent brain uptake of [3H]BNP by 1.5-fold. The increment of the BNP uptake by the brain suggests the involvement of a P-gp efflux mechanism of BNP transport at the BBB. [3H]BNP was eliminated with an apparent elimination half-life of 27.5 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [3H]BNP across the BBB was 0.154 ml/min/g brain, which was calculated from the elimination rate constant (2.52 x 10- 2 min- 1) and the distribution volume in the brain (6.11 ml/g brain). The efflux transport of [3H]BNP was inhibited by range from 32 to 64% in the presence of P-gp inhibitors. The present results suggest that BNP is transported from the brain across the BBB via a P-gp-mediated efflux transport system, at least in part.
Suzuki
Toyofumi
T
Department of Pharmaceutics, College of Pharmacy, Nihon University. 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan. t-suzuki@pha.nihon-u.ac.jp
Zaima
Chika
C
Moriki
Yoshiaki
Y
Fukami
Toshiro
T
Tomono
Kazuo
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002047:Buprenorphine / Q000097:blood / Q000493:pharmacokinetics*; D000440:Butanols / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007444:Inulin / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D000440:Butanols; D007202:Indicators and Reagents; D002047:Buprenorphine; D007444:Inulin