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Relationships Between Dosage, Serum Concentration, and Toxicity

Myron H. Jacobs, MD; Robert M. Senior, MD; Gerald Kessler, PhD

JAMA. 1976;235(18):1983-1986.

Abstract
Relationships between theophylline dosage, serum theophylline concentration, and theophylline toxicity were evaluated retrospectively in 47 hospitalized adults. The amount of theophylline administered daily varied more than sixfold, from 6 to 38 mg/kg. The serum theophylline concentrations, however, varied 24-fold from 2 to 49µg/ml. The relationship between daily dosage and serum concentration was unpredictable in an individual patient. Fourteen patients (30%) had a toxic reaction to theophylline. Toxic symptoms, which were not always gastrointestinal, occurred commonly with serum concentrations over 25µg/ml but were not noted with concentrations below 15µg/ml. High serum theophylline concentrations and a toxic reaction developed just as often with the oral route as when the drug was given intravenously. In six patients, measurement of serum theophylline concentration disclosed subtherapeutic concentrations. Serum theophylline determination appears to be important clinically in guiding effective and safe usage of theophylline.

(JAMA 235:1983-1986, 1976)

Author Affiliations
From the Pulmonary Disease and Respiratory Care Division, Department of Medicine (Drs Jacobs and Senior), and Department of Pathology Laboratory Medicine (Dr Kessler), Washington University School of Medicine at The Jewish Hospital of St Louis, St Louis. Dr Jacobs is now at the Pulmonary Division, Christian Hospital Northwest, St Louis.

Footnotes
Read in part before the Annual Meeting of the American Thoracic Society, Cincinnati, May 14, 1974.

Reprint requests to the Department of Medicine, The Jewish Hospital of St Louis, 216 S Kingshighway, St Louis, MO 63110 (Dr Senior).

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