QUANTIFICATION OF THEOPHYLLINE-INDUCED EOSINOPENIA AND HYPOKALEMIA IN HEALTHY-VOLUNTEERS

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 (C(max)) of 8.33 +/- 2.16 mg/L occurred 1.02 +/- 0.26h after ingestion. The delay between the C(max) and the subsequent eosinopenic or hypokalaemic 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 E(max) effect model. The maximal eosinopenic and hypokalaemic effects (E(max)) of the drug were 83 +/- 25.8% and 16 +/- 9.7% of the possible, respectively. The theophylline concentrations causing 50% of the E(max) (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.