Titre du document / Document title

The effect of three H₂ receptor antagonists on the disposition of cyclosporin A in the in situ perfused rat liver model

Auteur(s) / Author(s)

HUGHES C. M. ; SWANTON J. G. ; COLLIER P. S. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

Queen's univ. Belfast, school pharmacy, Belfast BT9 7BL, ROYAUME-UNI

Résumé / Abstract

The in situ perfused rat liver model was used to investigate the effect of three H₂ receptor antagonists on the disposition of cyclosporin A (CyA) and the major human metabolite, AM1. Perfusion experiments, using standard techniques, were carried out on four groups (one control and three H₂-receptor antagonist-treated groups) of male Sprague-Dawley rats (300-350g). All animals received CyA, 2.5 mg ; the three treated groups received cimetidine (8 mg), ranitidine (3 mg), or famotidine (0.4 mg). Perfusate and bile samples were collected and assayed for CyA, AM1, and the H₂ receptor antagonists by HPLC. Results indicated that CyA perfusate concentrations in the controls and cimetidine and ranitidine-treated groups were not significantly different, although levels in the famotidine group were significantly higher at all times (p < 0.05), except 30 min, compared to the controls. However, examination of the AMI perfusate and bile data and the apparent metabolic clearance data indicated that CyA metabolism was still occurring, despite the presence of the H₂ receptor antagonist. It is suggested that the absence of a interaction may be attributed to a lack of specificity of the H₂ receptor antagonists for CYP3A, the isoenzyme responsible for CyA metabolism.

Revue / Journal Title

Biopharmaceutics & drug disposition   ISSN 0142-2782   CODEN BDDID8 

Source / Source

1995, vol. 16, n^o9, pp. 719-733 (58 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley, Chichester, ROYAUME-UNI  (1979) (Revue)

Mots-clés anglais / English Keywords

Drug interaction ; Antihistaminic ; Pharmacokinetics ; Antagonist ; H2 receptor ; Drug combination ; Immunosuppressive agent ; Liver ; Rat ; Animal ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Famotidine ; Interaction médicamenteuse ; Ciclosporine ; Cimétidine ; Antihistaminique ; Ranitidine ; Pharmacocinétique ; Antagoniste ; Récepteur histaminergique H2 ; Association médicamenteuse ; Immunodépresseur ; Foie ; Rat ; Animal ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Interacción medicamentosa ; Antihistamínico ; Farmacocinética ; Antagonista ; Receptor histaminérgico H2 ; Asociación medicamentosa ; Inmunodepresor ; Hígado ; Rata ; Animal ; Rodentia ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 17959, 35400005993325.0010