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Titolo:
CONCENTRATION-DEPENDENT TUBULAR SECRETION OF ACETAZOLAMIDE AND ITS INHIBITION BY SALICYLIC-ACID IN THE ISOLATED-PERFUSED RAT-KIDNEY
Autore:
TAFT DR; CHAPRON DJ; FOURNIER DJ; SWEENEY KR;
Indirizzi:
LONG ISL UNIV,DIV PHARMAECUT & IND PHARM,1 UNIV PLAZA BROOKLYN NY 11201 UNIV CONNECTICUT,SCH PHARM STORRS CT 06269
Titolo Testata:
Drug metabolism and disposition
fascicolo: 4, volume: 24, anno: 1996,
pagine: 456 - 461
SICI:
0090-9556(1996)24:4<456:CTSOAA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
RENAL TRANSPORT KINETICS; ALBUMIN-BOUND SUBSTANCES; PROTEIN-BINDING; HEPATIC-UPTAKE; DISPOSITION; CLEARANCE; FLURBIPROFEN; RECEPTOR; HUMANS; DRUGS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
D.R. Taft et al., "CONCENTRATION-DEPENDENT TUBULAR SECRETION OF ACETAZOLAMIDE AND ITS INHIBITION BY SALICYLIC-ACID IN THE ISOLATED-PERFUSED RAT-KIDNEY", Drug metabolism and disposition, 24(4), 1996, pp. 456-461

Abstract

An isolated perfused rat kidney (IPK) technique was used to study theeffect of salicylic acid (SA) on the excretion of acetazolamide (AZ),Initial experiments were conducted in the absence of interactants at three nominal AZ concentrations (50, 100, and 250 mu g/ml). Over the concentration range studied, AZ demonstrated net tubular secretion in the IPK, Significant decreases in excretion ratio (4.97 +/- 0.79-2.66 +/- 1.1) and secretory clearance (0.809 +/- 0.23-0.541 +/- 0.28) were observed with increasing AZ concentration, consistent with saturation of tubular secretion, Using a facilitated model for renal secretion, values of tubular transport parameters were obtained from a plot of excretion ratio vs. unbound AZ concentration: t(max) = 118 +/- 29.4 mu g/min, K-M = 53.4 +/- 22.4 mu g/ml, and t(max(A)) = 6.31 +/- 2.82 mu g/min, In the presence of SA (200 mu g/ml), renal secretion of AZ was inhibited, as demonstrated by significant decreases in renal clearance (0.731 +/- 0.21-0.147 +/- 0.03) and excretion ratio (3.77 +/- 0.82-0.378 /- 0.07). Although these findings were indicative of a reabsorption component to AZ excretion in the IPK that had not been previously proposed, the results were consistent with a previous investigation of concomitant administration of AZ and SA in humans (Br. J. Clin, Pharmacol.27, 866, 1989), thereby endorsing utilization of the IPK as a screening tool for renal clearance mechanisms in humans.

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Documento generato il 17/01/21 alle ore 17:15:48