Interaction of famotidine with rat liver microsomes, a study showing less inhibition of drug metabolism than with cimetidine |
| |
| Authors: | Y Imai M Inada S Tamura S Noda S Kawata Y Minami S Tarui |
| |
| Affiliation: | 1. Translational Research Unit, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain;2. Instituto Aragonés de Ciencias de la Salud (IACS), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain;3. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain;4. Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain;5. Hematology Department, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain;6. Translational Research Unit-Río Hortega Grant, Miguel Servet University Hospital, P Isabel la Católica 1-3, 50009 Zaragoza, Spain;1. Sechenov First Moscow State Medical University, Moscow, Russia;2. Scientific Center for Expertise of Medical Products, Institute of Clinical Pharmacology, Moscow, Russia;3. AstraZeneca R&D, Mölndal, Sweden;4. World Health Organization (WHO), Geneva, Switzerland;5. Johannes Gutenberg-University, Mainz, Germany;6. University of Maryland, Baltimore, Maryland;7. International Pharmaceutical Federation (FIP), The Hague, The Netherlands;8. RIVM—National Institute for Public Health and the Environment, Bilthoven, The Netherlands;9. Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany |
| |
| Abstract: | ![]()
Interaction of famotidine with rat liver microsomes and its effect on drug metabolism in vitro were studied. Famotidine interacted with liver microsomes obtained from untreated, phenobarbital-pretreated and 3-methylcholanthrene-pretreated rats to produce characteristic type II spectral changes with peaks at 423-426 nm and troughs at 387-390 nm. The spectral dissociation constants were in the range of 0.84-0.94 mM. Famotidine inhibited aminopyrine N-demethylase activity to a much lesser extent than did cimetidine. The extent of inhibition at a concentration of 5 mM of famotidine was from 12 to 18% for the microsomes from the rats with different pretreatments. In contrast, 5 mM of cimetidine inhibited the activity 80, 59 and 80% in the microsomes from untreated, phenobarbital-pretreated and 3-methylcholanthrene-pretreated rats, respectively. Both famotidine and cimetidine inhibited aminopyrine N-demethylase in a mixed-type manner for the microsomes from phenobarbital-pretreated rats, with inhibition constants of 4.7 and 0.7 mM, respectively. These results demonstrate that famotidine is an in vitro inhibitor of microsomal drug metabolism in rats but is much less inhibitory than cimetidine. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
