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Titolo:
CHARACTERIZATION OF THE UPTAKE OF ROCURONIUM AND DIGOXIN IN HUMAN HEPATOCYTES - CARRIER SPECIFICITY AND COMPARISON WITH IN-VIVO DATA
Autore:
OLINGA P; MEREMA M; HOF IH; SLOOFF MJH; PROOST JH; MEIJER DKF; GROOTHUIS GMM;
Indirizzi:
UNIV GRONINGEN,CTR PHARM,DEPT PHARMACOKINET & DRUG DELIVERY,GRONINGENINST DRUG STUDIES NL-9713 AV GRONINGEN NETHERLANDS UNIV GRONINGEN HOSP,DEPT SURG,DIV HEPATOBILIARY SURG & LIVER TRANSPLANTAT NL-9713 EZ GRONINGEN NETHERLANDS
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 285, anno: 1998,
pagine: 506 - 510
SICI:
0022-3565(1998)285:2<506:COTUOR>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG TRANSPORT; HUMAN LIVER; METABOLISM; TRANSPLANTATION; OUABAIN; QUININE; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
P. Olinga et al., "CHARACTERIZATION OF THE UPTAKE OF ROCURONIUM AND DIGOXIN IN HUMAN HEPATOCYTES - CARRIER SPECIFICITY AND COMPARISON WITH IN-VIVO DATA", The Journal of pharmacology and experimental therapeutics, 285(2), 1998, pp. 506-510

Abstract

Mechanisms of drug transport in the liver have been investigated predominantly in rodents. Most of the in vitro drug research in the liver is performed in liver preparations of animals. The results of such experiments frequently are discussed in relation to anticipated metabolicprofiles in man, but these extrapolations are often inappropriate because of large interspecies differences in drug metabolism. In the present study, the mechanisms and specificity of the uptake of the organiccation rocuronium and the cardiac glycoside digoxin were investigatedin human hepatocytes and were compared with results obtained in rat hepatocytes. The extraction ratio for the intact liver was calculated from the measured uptake rates of the compounds in the human cells in vitro and compared with published in vivo data. The initial hepatic extraction ratio, calculated from the in vitro uptake data for digoxin and rocuronium, very well reflected the initial extraction ratio for distribution in the liver in vivo in man. Uptake of 100 mu M rocuronium was inhibited by 40 mu M K-strophantoside (80% inhibition), and although not significantly, by 160 mu M procainamide ethobromide, whereas no inhibitory effect was found in the presence of 160 mu M taurocholic acid. In a previous study in rat hepatocytes, marked inhibition of digoxin uptake by quinine and only minimal inhibition by the diastereomer quinidine was demonstrated, showing clear stereoselectivity in transport inhibition. Unexpectedly. the uptake of digoxin in human hepatocyteswas not inhibited significantly by quinidine or quinine, which indicates clear species differences. This is the first study to investigate the uptake mechanisms of organic cations and cardiac glycosides in human hepatocytes in some detail. The results show that uptake characteristics of drugs found in rats can not be extrapolated directly to humans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 05:05:28