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Titolo:
Cellular distribution and handling of liver-targeting preparations in human livers studied by a liver lobe perfusion
Autore:
Melgert, BN; Olinga, P; Weert, B; Slooff, MJH; Meijer, DKF; Poelstra, K; Groothuis, GMM;
Indirizzi:
Univ Groningen, Inst Drug Explorat, Dept Pharmacokinet & Drug Delivery, NL-9700 AB Groningen, Netherlands Univ Groningen Groningen Netherlands NL-9700 AB B Groningen, Netherlands Univ Groningen Hosp, Dept Surg, Div Hepatobiliary Surg & Liver Transplantat, Groningen, Netherlands Univ Groningen Hosp Groningen Netherlands antat, Groningen, Netherlands
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 4, volume: 29, anno: 2001,
pagine: 361 - 367
SICI:
0090-9556(200104)29:4<361:CDAHOL>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-LIVER; ENDOTHELIAL-CELLS; HUMAN HEPATOCYTES; SLICES; DRUGS; ENDOCYTOSIS; CIRRHOSIS; ALBUMIN; INVIVO; TRANSPLANTATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Melgert, BN Ant Deusinglaan 1, NL-9713 AV Groningen, Netherlands Ant Deusinglaan 1 Groningen Netherlands NL-9713 AV therlands
Citazione:
B.N. Melgert et al., "Cellular distribution and handling of liver-targeting preparations in human livers studied by a liver lobe perfusion", DRUG META D, 29(4), 2001, pp. 361-367

Abstract

We developed and tested a novel method for perfusing parts of human liver to study uptake and handling of drug-targeting preparations. These preparations, designed for the treatment of liver fibrosis in man, have been extensively studied in animals, but little is known about the uptake and handlingby human livers. Human liver tissue was obtained from livers procured frommultiorgan donors and from cirrhotic livers of patients. To assess tissue viability, perfusate glutamate-oxalacetate-transaminase (GOT), glutamate-pyruvate-transaminase (GPT), and lactate dehydrogenase (LDH) levels were determined. To assess tissue functionality, the uptake of taurocholic acid and phase I and II metabolism of lidocaine and 7-hydroxycoumarin were determined. Uptake of a drug-targeting preparation was studied with Dexa(10)-HSA, which is designed for targeting of dexamethasone to nonparenchymal cells in the liver. During a 90-min perfusion period, no elevation of either GOT, GPT, or LDH was found. Both healthy control livers and cirrhotic livers showedphase I and II drug metabolism and functional taurocholic acid uptake. Studies with Dexa(10)-HSA revealed that 60 min after administration, 40% of the dose had been taken up by control livers and only 5% by cirrhotic livers. In control livers, Kupffer and endothelial cells had taken up Dexa(10)-HSA, whereas in cirrhotic livers only Kupffer cells were responsible for the uptake. Viability parameters and liver function tests clearly showed the applicability of this method. In the perfusion set-up, we showed uptake of thedrug-targeting preparation Dexa(10)-HSA by healthy and cirrhotic human liver tissue, although the distribution patterns differed. This demonstrates the need to study new concepts in (diseased) human tissue.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 18:10:59