Linked Life Data

10383920

Source:http://linkedlifedata.com/resource/pubmed/id/10383920

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-20
pubmed:abstractText
This in vitro study was designed to identify the enzyme(s) involved in the two major metabolic pathways of rokitamycin [formations of leucomycin A7 (LMA7) from rokitamycin and of leucomycin V (LMV) from LMA7] and to assess possible drug interactions using human liver microsomes. Formation of LMA7 or LMV was NADPH-independent. Anti-rat NADPH cytochrome P-450 (CYP) reductase serum, specific inhibitors, or substrates of CYP isoforms showed no effects on the formation of LMA7 or LMV. The mean Vmax and Vmax/Km for the formation of LMA7 from rokitamycin were much greater (P <.01) than those for the formation of LMV from LMA7. Two esterase inhibitors, bis-nitro-phenylphosphate and physostigmine (100 microM), inhibited the formation of LMA7 or LMV by more than 85%, whereas no appreciable inhibition occurred by several substrates of carboxylesterase (EC 3.1.1.1). Except the moderate inhibition produced by promethazine and terfenadine, theophylline, mequitazine, chlorpheniramine, and diphenhydramine showed little or no inhibition for the formation of LMA7 or LMV. Rokitamycin, LMA7, LMV, erythromycin, and clarithromycin (up to 500 microM) had no appreciable inhibition for CYP1A2-, 2C9-, and 2D6-mediated catalytic reactions. However, rokitamycin, LMA7, erythromycin, and clarithromycin inhibited the CYP3A4-catalyzed triazolam alpha-hydroxylation with IC50 (Ki) values of 5.8 (2.0), 40, 33 (20), and 56 (43) microM, respectively. It is concluded that the formations of LMA7 from rokitamycin and of LMV from LMA7 are catalyzed mainly by human esterase enzyme [possibly cholinesterase (EC3.1.1.8)]. However, whether rokitamycin would inhibit the CYP3A-mediated drug metabolism in vivo requires further investigations in patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
776-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
An in vitro study on the metabolism and possible drug interactions of rokitamycin, a macrolide antibiotic, using human liver microsomes.
pubmed:affiliation
Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't