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Titolo:
THE STEREOISOMERS QUININE AND QUINIDINE EXHIBIT A MARKED STEREOSELECTIVITY IN THE INHIBITION OF HEPATOBILIARY TRANSPORT OF CARDIAC-GLYCOSIDES
Autore:
HEDMAN A; MEIJER DKF;
Indirizzi:
UNIV GRONINGEN,UNIV CTR PHARM,DEPT PHARMACOKINET & DRUG DELIVERY,GRONINGEN INST DRUG STUDIES NL-9713 AV GRONINGEN NETHERLANDS UNIV GRONINGEN,UNIV CTR PHARM,DEPT PHARMACOKINET & DRUG DELIVERY,GRONINGEN INST DRUG STUDIES NL-9713 AV GRONINGEN NETHERLANDS
Titolo Testata:
Journal of hepatology
fascicolo: 2, volume: 28, anno: 1998,
pagine: 240 - 249
SICI:
0168-8278(1998)28:2<240:TSQAQE>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC ANION TRANSPORTER; BILIARY ELIMINATION; BASIC DRUGS; DIGOXIN; CLEARANCE; LIVER; HEPATOCYTES; SECRETION; HUMANS; BILE;
Keywords:
DIGOXIN; HEPATOBILIARY TRANSPORT; OUABAIN; QUININE; QUINIDINE; RAT LIVER; STEREOSELECTIVE INTERACTIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
A. Hedman e D.K.F. Meijer, "THE STEREOISOMERS QUININE AND QUINIDINE EXHIBIT A MARKED STEREOSELECTIVITY IN THE INHIBITION OF HEPATOBILIARY TRANSPORT OF CARDIAC-GLYCOSIDES", Journal of hepatology, 28(2), 1998, pp. 240-249

Abstract

Background / Aims: Certain basic (cationic) drugs are known to interact with the hepatic transport, and renal and/or biliary clearance of cardia glycosides. The mechanisms behind these interactions are not fully understood, In the present study our was to investigate the effectsof the two diastereomers, quinidine and quinine, as well as the calcium antagonist verapamil, on the hepatobiliary elimination of digoxin and ouabain in the isolated perfused rat liver. Methods: Livers from male, fasting Wistar rats were perfused by recirculation of Krebs-Henseleit bicarbonate buffer supplemented with 1% BSA. Disposition of digoxin or ouabain was studied at an initial perfusion medium concentration (C-i) of 100 or 10 nmol/l for digoxin and a C-i of 30 mu mol/l for ouabain. The C-i of quinine, quinidine or verapamil was 50 mu mol/l. Concentrations of the drugs in perfusion medium and bile were followed up to 2 h. Results: A marked reduction in the initial medium disappearance rate of digoxin and ouabain by quinine was found, whereas quinidine did not affect the hepatic disposition of the cardiac glycosides, The stereoselective inhibition of digoxin and ouabain clearance by quinine, and not by quinidine, was shown to be due to an effect on the hepatic uptake level rather than on the metabolic conversion and/or the biliary excretion steps, An allosteric type of inhibition by the basic drugs, exerted from the inside of the cells, is inferred, The's interaction may occur at the sinusoidal plasma membrane on the level of multi-specific carrier proteins far cardiac glycosides and cationic drugs, ascloned recently by various groups. Conclusions: A marked stereoselective differences was found in the effect of the stereoisomers quinidineand quinine on the hepatic uptake of digoxin and ouabain, quinine being the potent inhibitor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 21:55:18