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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.
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
May 2006,
Journal of acquired immune deficiency syndromes (1999),
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
January 2014,
Drug design, development and therapy,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
January 1983,
Clinical and experimental neurology,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
July 2005,
Journal of clinical pharmacology,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
October 2003,
Journal of clinical pharmacology,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
November 2018,
Cancer chemotherapy and pharmacology,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
January 1983,
Clinical pharmacy,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
January 1980,
International journal of clinical pharmacology, therapy, and toxicology,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
June 1990,
Transplantation proceedings,
J M Kovarik, and
E A Mueller, and
M Gaber, and
A Johnston, and
E Jähnchen
March 2010,
HIV medicine,
