Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IN-VITRO METABOLISM OF CYCLOSPORINE-A WITH RABBIT RENAL OR HEPATIC MICROSOMES - ANALYSIS BY HPLC-FPIA AND HPLC-MS
Autore:
PHAMHUY C; SADEG N; BECUE T; MARTIN C; MAHUZIER G; WARNET JM; HAMON M; CLAUDE JR;
Indirizzi:
UNIV PARIS 05,FAC PHARM,TOXICOL LAB,EA 207 F-75270 PARIS 06 FRANCE UNIV PARIS 11,CHIM ANALYT LAB F-92270 CHATENAY MALABRY FRANCE
Titolo Testata:
Archives of toxicology
fascicolo: 5, volume: 69, anno: 1995,
pagine: 346 - 349
SICI:
0340-5761(1995)69:5<346:IMOCWR>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIQUID-CHROMATOGRAPHY; DRUG-INTERACTIONS; CLINICAL UTILITY; CYTOCHROME-P-450; RECIPIENTS; TRANSPLANT; BLOOD; ASSAY;
Keywords:
IN VITRO METABOLISM; CYCLOSPORINE A; RENAL AND HEPATIC MICROSOMES; HPLC-MASS SPECTROMETRY; FPIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
16
Recensione:
Indirizzi per estratti:
Citazione:
C. Phamhuy et al., "IN-VITRO METABOLISM OF CYCLOSPORINE-A WITH RABBIT RENAL OR HEPATIC MICROSOMES - ANALYSIS BY HPLC-FPIA AND HPLC-MS", Archives of toxicology, 69(5), 1995, pp. 346-349

Abstract

Cyclosporin A (CsA) is in vivo mainly metabolized by hepatic cytochrome P450 IIIA to more than 21 metabolites, the major ones known as: M1,M17 and M21. The aim of this work is to explore the in vitro metabolism of CsA after incubation, in the presence of NADPH, with renal or hepatic microsomes obtained from rabbits pretreated with rifampycin (enzyme inducer) or erythromycin (enzyme inhibitor). The presumed metabolites were separated by semi-preparative high-performance liquid chromatography (HPLC) and identified in each collected fraction by fluorescence polarization immunoassay (FPIA) (HPLC-FPIA) using a non-specific polyclonal antibody. They were also analyzed by HPLC-mass spectrometry (MS) using fast atom bombardment (HPLC-MS-FAB). Five collected fractions gave positive results with FPIA. The major metabolites found were M1, M17 and M21 after identification by HPLC-MS-FAB and comparison with three corresponding standard metabolites. The CsA biotransformation rates were calculated by the amount of unmetabolized CsA and were linearwith time. These mean rates (V-m) for 12-min incubation by renal microsomes of rabbits treated with rifampicin or erythromycin or untreated(control) were 0.11, 0.02 and 0.04 nmol/min x mg microsomal protein, respectively. These rates were 15-, 37-, and 30-fold lower than those obtained with hepatic microsomes of rabbits treated identically. As CsA metabolites are less cytotoxic than the parent drug, this weak renalbiotransformation of CsA after in vitro incubation should be one of the mechanisms of its in vivo nephrotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:49:02