Relationship between lipophilicity and tubular reabsorption for a series of 5-alkyl-5-ethylbarbituric acids in the isolated perfused rat kidney preparation.
The renal clearances of a homologous series of six 5-substituted barbituric acids, of varying lipophilicity, were examined using a recirculating isolated perfused rat kidney preparation. Renal clearance was found to decrease with increasing lipophilicity. The renal clearance of the individual compounds was shown to be dependent on urine flow, with the dependence increasing with increasing lipophilicity. A simple physiologically based model of tubular reabsorption, evoking nonequilibrium permeability considerations, is used to explain this influence of urine flow on renal clearance. The relationship between clearance and tubular permeability was examined with the purpose of integrating lipophilicity into the model.
Mayer
J M
JM
Department of Pharmacy, University of Manchester, U.K.
Hall
S D
SD
Rowland
M
M
D000818:Animals; D001463:Barbiturates / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism
D001463:Barbiturates; D005947:Glucose; D010130:p-Aminohippuric Acid