Quantification of theophylline-induced eosinopenia and hypokalaemia 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 250 mg. The mean peak theophylline concentration (Cmax) of 8.33 +/- 2.16 mg/L occurred 1.02 +/- 0.26 h after ingestion. The delay between the Cmax and the subsequent eosinopenic or hypokalaemic nadirs was 4.52 +/- 1.73 and 3.65 +/- 1.32 h, 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.
Braat
M C
MC
Department of Pulmonology, University of Amsterdam, The Netherlands.
Jonkers
R E
RE
Bel
E H
EH
Van Boxtel
C J
CJ
D000328:Adult; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced* / Q000378:metabolism; D007970:Leukopenia / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D013806:Theophylline