Linked Life Data

9466344

Source:http://linkedlifedata.com/resource/pubmed/id/9466344

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-3-17
pubmed:abstractText
The purpose of this study was to evaluate possible interaction of nifedipine with erythromycin or rokitamycin in the intestinal mucosa. Male beagle dogs were orally administered nifedipine (10 mg), with or without oral pre-medication with erythromycin (300 mg), and 300 mg erythromycin or rokitamycin twice a day for 3 days. The experiments were of randomized cross-over design with a two-week wash-out period between dosing regimens. Erythromycin pre-medication for 3 days resulted in a significant increase in the area under the serum nifedipine concentration-time curve (AUC), whereas the curve for one nifedipine metabolite (M-2) decreased significantly. When the effects of erythromycin on the metabolism of nifedipine were studied using dog liver microsomes it was found that erythromycin significantly inhibited formation of M-2 but not of the metabolite M-1. These results indicate that formation of M-2 from M-1 in the liver might be reduced by erythromycin pre-medication. To avoid possible metabolism in the gut, the dogs were then administered 8 mg nifedipine into the peritoneal cavity, with or without multiple dose pre-treatment with erythromycin for 3 days. After intraperitoneal administration of nifedipine, the maximum concentration (Cmax) of nifedipine increased significantly. After pre-administration of erythromycin the relative bioavailability of nifedipine after oral administration was increased compared with injection into the peritoneal cavity. In-vitro study using rat intestinal microsomes and the in-vivo rat intestinal loop technique also showed that pre-administration of erythromycin inhibits nifedipine metabolism in the small intestine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3573
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1205-10
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9466344-Animals, pubmed-meshheading:9466344-Anti-Bacterial Agents, pubmed-meshheading:9466344-Area Under Curve, pubmed-meshheading:9466344-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:9466344-Biological Availability, pubmed-meshheading:9466344-Calcium Channel Blockers, pubmed-meshheading:9466344-Cytochrome P-450 CYP3A, pubmed-meshheading:9466344-Cytochrome P-450 Enzyme System, pubmed-meshheading:9466344-Dogs, pubmed-meshheading:9466344-Drug Interactions, pubmed-meshheading:9466344-Erythromycin, pubmed-meshheading:9466344-Intestine, Small, pubmed-meshheading:9466344-Kinetics, pubmed-meshheading:9466344-Liver, pubmed-meshheading:9466344-Male, pubmed-meshheading:9466344-Microsomes, pubmed-meshheading:9466344-Miocamycin, pubmed-meshheading:9466344-Nifedipine, pubmed-meshheading:9466344-Oxidoreductases, N-Demethylating, pubmed-meshheading:9466344-Portal Vein, pubmed-meshheading:9466344-Rats, pubmed-meshheading:9466344-Rats, Wistar
pubmed:year
1997
pubmed:articleTitle
Inhibition of nifedipine metabolism in dogs by erythromycin: difference between the gut wall and the liver.
pubmed:affiliation
Department of Pharmacy, Kumamoto University Hospital, Japan.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro