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The mechanism of cyclosporine toxicity induced by clarithromycin
Author(s) -
Spicer S. T.,
Liddle C.,
Chapman J. R.,
Barclay P.,
Nankivell B. J.,
Thomas P.,
O'Connell P. J.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.54310.x
Subject(s) - clarithromycin , cyp3a , drug interaction , toxicity , pharmacology , medicine , erythromycin , gastroenterology , ciclosporin , pharmacokinetics , cytochrome p450 , transplantation , antibiotics , biology , metabolism , microbiology and biotechnology , helicobacter pylori
Aims Recently a number of case reports have described the interaction of clarithromycin with cyclosporine A, resulting in cyclosporine toxicity. This interaction is presumed to take place via the hepatic cytochrome P450 enzyme system. Methods Following a case of cyclosporine toxicity and acute renal failure in a transplant patient started on clarithromycin, we investigated the effect of oral clarithromycin on the hepatic P450 system in five healthy normal male volunteers, by means of the erythromycin breath test. Results Cytochrome P4503A (CYP3A) activity was reduced in all subjects by a mean level of 26% following clarithromycin treatment. This would result in a significant reduction in cyclosporine clearance in patients receiving clarithromycin. Conclusions As clarithromycin was shown to inhibit CYP3A activity in all subjects tested, we recommend that a high degree of caution be exercised when clarithromycin is administered to patients receiving cyclosporine therapy or other drugs known to be eliminated by CYP3A‐mediated metabolism.