Stereoselective inhibition of renal organic cation transport in human kidney.
Amantadine was found to be concentrated by human cortical slices, with apparent Km and Vmax values of 187 +/- 11 microM and 1.37 +/- 0.28 nmol mg-1 min-1 respectively (mean +/- s.e. mean, n = 4). Addition of quinine (8S, 9R-(-)-isomer) or quinidine (8R, 9S-(+)-isomer) competitively inhibited this accumulation (apparent Ki values of 261 +/- 44 (n = 4) and 586 +/- 68 microM (n = 3), respectively). The stereoselectivity of this inhibition is the reverse of that seen with respect to the renal clearances of the diastereoisomers.
Wong
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Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Smyth
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D000328:Adult; D000368:Aged; D000547:Amantadine / Q000493:pharmacokinetics; D000818:Animals; D002412:Cations / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism
D002412:Cations; D011803:Quinine; D000547:Amantadine; D011802:Quinidine