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Quantification of Theophylline-Induced Eosinopenia and Hypokalaemia in Healthy Volunteers

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Summary

The relationship between theophylline pharmacokinetics and its eosinopenic and hypokalaemic effects were studied in 6 healthy volunteers after an oral dose of theophylline 250mg. The mean peak theophylline concentration (Cmax) of 8.33 ±2.16 mg/L occurred 1.02 ± 0.26h after ingestion. The delay between the Cmax and the subsequent eosinopenic or hypokalemic nadirs was 4.52 ± 1.73 and 3.65 ± 1.32h, respectively. The time courses of theophylline and its effects were linked by a sigmoid Emax effect model. The maximal eosinopenic and hypokalaemic effects (Emax) of the drug were 83 ± 25.8% and 16 ± 9.7% of the possible, respectively. The theophylline concentrations causing 50% of the Emax (EC50) were 5.06 ± 1.84 and 5.04 ± 2.09 mg/L, respectively. The data obtained with our methodology indicate that, in humans, theophylline induced eosinopenia could be mediated through a receptor and/or postreceptor mechanism unrelated to the mechanism of theophylline induced bronchodilation. We conclude that therapeutic theophylline plasma concentrations have a profound effect on the redistribution of blood eosinophils.

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Authors and Affiliations

  1. Departments of Pulmonology and Clinical Pharmacology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    M. C. Paul Braat, Rene E. Jonkers, Elisabeth H. Bel & Chris J. Van Boxtel

  2. Department of Pulmonology, Academic Hospital University of Leiden, Leiden, The Netherlands

    M. C. Paul Braat, Rene E. Jonkers, Elisabeth H. Bel & Chris J. Van Boxtel

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  1. M. C. Paul Braat
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  2. Rene E. Jonkers
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  3. Elisabeth H. Bel
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  4. Chris J. Van Boxtel
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Braat, M.C.P., Jonkers, R.E., Bel, E.H. et al. Quantification of Theophylline-Induced Eosinopenia and Hypokalaemia in Healthy Volunteers. Clin. Pharmacokinet. 22, 231–237 (1992). https://doi.org/10.2165/00003088-199222030-00005

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