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Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine
Author(s) -
Stein C. Michael,
Kinirons Mark T.,
Pincus Theodore,
Wilkinson Grant R.,
Wood Alastair J. J.
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90023-5
Subject(s) - erythromycin , rheumatoid arthritis , dapsone , cyp3a , pharmacology , in vivo , medicine , chemistry , gastroenterology , antibiotics , biology , immunology , metabolism , cytochrome p450 , biochemistry , microbiology and biotechnology
Cytochrome P4503A (CYP3A) is primarily responsible for the metabolism of cyclosporine and that of many other drugs. Several substrates of CYP3A have been investigated for use as pharmacologic probes to predict the CYP3A‐metabolizing capacity of an individual and, therefore, the disposition of other CYP3A substrate drugs. One such measure of CYP3A activity is the 14 C erythromycin breath test, which has been applied to the prediction of cyclosporine disposition. However, the test has practical limitations. Because of this, the 0‐ to‐8‐hour urinary dapsone recovery ratio has been studied as an alternative and more practical probe of CYP3A activity. Methods The dapsone recovery ratio and the 14 C erythromycin breath test were correlated with cyclosporine concentrations in 16 patients with rheumatoid arthritis to determine the usefulness of the dapsone recovery ratio as an alternative to the 14 C erythromycin breath test. The erythromycin breath test showed a fourfold variation between subjects and correlated weakly with trough cyclosporine concentrations ( r = −0.50, P < 0.05), whereas the dapsone recovery ratio varied only approximately twofold between subjects and did not correlate with trough cyclosporine concentrations ( r = 0.02, p = 0.94). The correlation between the dapsone recovery ratio and the erythromycin breath test ( r = 0.22, p = 0.41) was not significant. Conclusions These data suggest that results obtained with one probe in vivo may not apply to another CYP3A substrate. The poor quantitative relationship between cyclosporine concentrations and the erythromycin breath test limits its usefulness in the prediction of an individual's cyclosporine dose requirement Clinical Pharmacology & Therapeutics (1996) 59 , 47–51; doi: