Linked Life Data

11583481

Source:http://linkedlifedata.com/resource/pubmed/id/11583481

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-10-3
pubmed:abstractText
Rofecoxib is a highly selective and potent inhibitor of cyclooxgenase-2 (COX-2). Methotrexate is a disease-modifying agent with a narrow therapeutic index frequently prescribed for the management of rheumatoid arthritis. The objective of this study was to investigate the influence of clinical doses of rofecoxib on the pharmacokinetics of methotrexate in patients with rheumatoid arthritis. This was a randomized, double-blind, placebo-controlled study in 25 rheumatoid arthritis patients on stable doses of methotrexate. Patients received oral methotrexate (7.5 to 20 mg) on days -1, 7, 14, and 21. Nineteen patients received rofecoxib 12.5, 25, and 50 mg once daily on days 1 to 7, 8 to 14, and 15 to 21, respectively. Six patients received placebo on days 1 to 21 only to maintain a double-blinded design for assessment of adverse experiences. Plasma and urine samples were analyzed for methotrexate and its major although inactive metabolite, 7-hydroxymethotrexate. The AUC(0-infinity) geometric mean ratios (GMR) and their 90% confidence intervals (90% CI) (rofecoxib + methotrexate/methotrexate alone) for day 7/day -1, day 14/day -1, and day 21/day -1, for rofecoxib 12.5, 25, and 50 mg, were 1.03 (0.93, 1.14), 1.02 (0.92, 1.12), and 1.06 (0.96, 1.17), respectively (p > 0.2 for all comparisons to day -1). All AUC(0-infinity), GMR and Cmax GMR 90% CIs fell within the predefined comparability limits of (0.80, 1.25). Similar results were observed for renal clearance of methotrexate and 7-hydroxymethotrexate at the highest dose of rofecoxib tested (50 mg). It was concluded that rofecoxib at doses of 12.5, 25, and 50 mg once daily has no effect on the plasma concentrations or renal clearance (tested at the highest dose of rofecoxib) of methotrexate in rheumatoid arthritis patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1120-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11583481-Adult, pubmed-meshheading:11583481-Aged, pubmed-meshheading:11583481-Analysis of Variance, pubmed-meshheading:11583481-Antirheumatic Agents, pubmed-meshheading:11583481-Area Under Curve, pubmed-meshheading:11583481-Arthritis, Rheumatoid, pubmed-meshheading:11583481-Confidence Intervals, pubmed-meshheading:11583481-Cyclooxygenase Inhibitors, pubmed-meshheading:11583481-Dose-Response Relationship, Drug, pubmed-meshheading:11583481-Double-Blind Method, pubmed-meshheading:11583481-Drug Interactions, pubmed-meshheading:11583481-Female, pubmed-meshheading:11583481-Folic Acid Antagonists, pubmed-meshheading:11583481-Humans, pubmed-meshheading:11583481-Lactones, pubmed-meshheading:11583481-Male, pubmed-meshheading:11583481-Methotrexate, pubmed-meshheading:11583481-Middle Aged, pubmed-meshheading:11583481-Sulfones
pubmed:year
2001
pubmed:articleTitle
Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthritis patients.
pubmed:affiliation
Clinical Pharmacology Department, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Multicenter Study