Document Detail


Pharmacokinetics of cyclosporine and steady-state aspirin during coadministration.
MedLine Citation:
PMID:  8366176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Anecdotal reports from clinical trials assessing the use of cyclosporine in the treatment of rheumatoid arthritis suggest an association between enhanced renal impairment and combined use of cyclosporine with nonsteroidal anti-inflammatory drugs. To explore possible pharmacokinetic contributions to this phenomenon, a randomized, two-period crossover investigation was performed in 24 healthy volunteers in which a single oral dose of 300 mg cyclosporine was administered alone and on day 10 of multiple oral dosing of aspirin 960 mg three times daily. Serial blood samples were obtained over 48 hours after each cyclosporine dose and over a steady-state dosing interval for aspirin on day 9 (aspirin alone) and day 10 (coadministration of cyclosporine and aspirin). Cyclosporine whole blood concentrations were determined by a specific monoclonal radioimmunoassay and plasma concentrations of acetylsalicylic acid and metabolites by high-performance liquid chromatography. Lack of a pharmacokinetic interaction was conclusively demonstrated for the rate and extent of cyclosporine and acetylsalicylic acid absorption and for the rate and extent of salicylic acid formation after a single dose of cyclosporine was coadministered during steady-state aspirin dosing. If a clear association between enhanced renal impairment and the combined use of cyclosporine and aspirin is substantiated, the underlying mechanism appears to be pharmacodynamic rather than pharmacokinetic.
Authors:
J M Kovarik; E A Mueller; M Gaber; A Johnston; E Jähnchen
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  33     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-10-04     Completed Date:  1993-10-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  513-21     Citation Subset:  IM    
Affiliation:
Department of Human Pharmacology, Sandoz Pharma, Ltd., Basle, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aspirin / administration & dosage,  pharmacokinetics*
Cyclosporine / administration & dosage,  pharmacokinetics*
Drug Interactions
Half-Life
Humans
Male
Metabolic Clearance Rate
Chemical
Reg. No./Substance:
50-78-2/Aspirin; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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