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• W1483807744 abstract "To examine whether inhibition of P-glycoprotein (P-gp) activity by quinidine affects the central nervous system toxicity of lidocaine and racemic bupivacaine (bupivacaine).Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10). Fifteen minutes following administration of 15 mg x kg(-1) of quinidine (QL and QB groups) or saline (L and B groups), lidocaine (L and QL groups, 4 mg x kg(-1) x min(-1)) or bupivacaine (B and QB groups, 1 mg x kg(-1) x min(-1)) was infused until convulsions occurred. Concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) and bupivacaine in plasma and in the brain at the onset of convulsions were measured by high-performance liquid chromatography.There were no differences in the dose of lidocaine required to induce convulsions between the L and QL groups. There were no differences in the concentrations of total (L = 17.2 +/- 3.5, QL = 16.6 +/- 2.6 micro g x mL(-1)) or unbound lidocaine (L = 7.8 +/- 2.5, QL = 7.3 +/- 2.3 micro g x mL(-1)), total (L = 1.2 +/- 0.5, QL = 1.3 +/- 0.7 micro g x mL(-1)) or unbound MEGX (L = 0.9 +/- 0.5, QL = 0.8 +/- 0.4 micro g x mL(-1)) in plasma, total lidocaine or MEGX in the brain at the onset of convulsions between the L and QL groups. The dose of bupivacaine required to induce convulsions was comparable in the B and QB groups. At the onset of convulsions, plasma concentrations of both total (B = 4.9 +/- 1.1, QB = 4.0 +/- 0.6 micro g x mL(-1), P = 0.03) and unbound bupivacaine (B = 1.4 +/- 0.6, QB = 0.9 +/- 0.2 micro g x mL(-1), P = 0.02) were significantly lower in the QB group than in the B group. There were no differences in concentration of total bupivacaine in the brain between the B and QB groups.These results suggest that quinidine inhibited P-gp activity, resulting in increased brain/plasma concentration ratio of bupivacaine, but not of lidocaine, and decreased the threshold of plasma concentration for bupivacaine-induced convulsions." @default.
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• W1483807744 date "2003-10-01" @default.
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• W1483807744 title "The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats" @default.
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• W1483807744 doi "https://doi.org/10.1007/bf03019376" @default.
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