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  • Title: Theophylline for chronic asthma: rationale for treatment, product selection, and dosage schedule.
    Author: Weinberger M, Hendeles L.
    Journal: Pediatr Pharmacol (New York); 1983; 3(3-4):273-85. PubMed ID: 6429620.
    Abstract:
    Although theophylline has been available for over 50 years, only in the last 10 years has an understanding of its pharmacodynamics and pharmacokinetics permitted its use with optimal efficacy and safety. Serum concentrations between 10 and 20 mcg/ml stabilize the hyperreactive airways that characterize asthma as measured by exercise-induced bronchospasm and clinical suppression of asthmatic symptoms, even among those patients not sufficiently controlled with bronchodilators alone who consequently require inhaled or oral corticosteroid therapy. Careful dosage titration prevents adverse effects, especially when final dosage is guided by measurement of serum concentration. Large interpatient variability in dose requirements is seen, but there is normally little intrapatient variability except when physiologic abnormalities or drug interactions alter the elimination of theophylline. Rapid elimination, rapid absorption from conventional products, and the narrow therapeutic range for theophylline result in clinically important fluctuations in serum concentration and consequent effect unless unrealistically short dosing intervals are maintained or reliable slow-release formulations are used. Slow-release theophylline products vary, however, and performance often does not match the manufacturer's claims. Assessment requires characterization of absorption rate, which then allows prediction of fluctuations in serum concentration at specified dose intervals and defined rates of elimination.
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