| OBSERVATION'S |
Theophylline is a methylxanthine used to treat bronchospasm, including asthma, and obstructive airway disease.1,2 Its effectiveness as a bronchodilator agent overrides the low margin of safety between its effective therapeutic level and the onset of toxicity symptoms.1 Theophylline is completely and rapidly absorbed from the gastro-intestinal tract, with an oral dose being absorbed in one hour and peak plasma concentrations being achieved in two hours.3-5 The drug is widely distributed in body fluids. In plasma about forty percent is protein bound.6 Theophylline is eliminated from the body via several parallel pathways. Approximately ten percent is eliminated unchanged by the kidneys, while the remainder is metabolized, apparently in the liver, largely to uric acid derivatives and 3-methylxanthine.2,6-8 Theophylline has a narrow therapeutic index with a range for serum levels from 10-20ug/ml.6,9,10 Individualized dosing and routine serum level monitoring are necessary for patients receiving theophylline, due to wide variation in theophylline absorption, metabolism and clearance.6,9,10 Weinberger M, Hendeles L, Johnson G. Rationale of procedures for monitoring serum theophylline levels. In: Baer DM ed. Technical Improvement Service, American Society of Clinical Pathologists. Chicago, 1978;3. Bierman CW, Williams, PV. Therapeutic monitoring of theophylline. Rationale and current status. Clin Pharmacokinet 1989; 17(6): 377-384. Mitenko Pa, Ogilvie RI. Pharmacokinetics of intravenous theophylline. Clin Pharmacol Ther 1973; 14: 509-513. Hendeles L, Weinberer M, Bighley L. Disposition of theophylline following a single intravenous aminophylline infusion. Am Rev Respir Dis 1978; 118: 97-103. Aranda JV, et al. Pharmacokinetic aspects of theophylline in premature newborns. N Eng J Med 1976; 295: 413-416. Rowe DJ, Watson ID, Williams J, Berry DJ. The clinical use and measurement of theophylline. Ann Clin Biochem 1988; 25: 4-26. Ogilvie RJ. Clinical pharmacokinetics of theophylline. Clin Pharmacokinet 1978; 3: 267-293. Levy G, Koysooko R. Renal clearance of theophylline in man. J Clin Pharmacol 1976; 16: 329-332. Jenne JW, Wyze E, Rood FS, MacDonald RM. Pharmacokinetics of theophylline: application to adjustment of the clinical dose of aminophylline. Clin Pharmacol Ther 1972; 13: 349-360. Sessler CN. Theophylline toxicity: clinical features of 116 consecutive cases. American Journal of Medicine 1990; 88(6): 567-576. |
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