Oral sustained‐release aminophylline in medical inpatients: factors related to toxicity and plasma theophylline concentrations.

Abstract

1 Consecutive medical inpatients expected to benefit from a theophyllinate were treated with sustained-release aminophylline in a protocol conforming with ordinary practice. Of 16 patients, five had toxicity with aminophylline 450 mg daily, and a further three with 900 mg daily. Toxicity was serious in three patients. 2 Toxicity was significantly less common in cigarette smokers, and was related to higher plasma theophylline concentrations. However, there was a large overlap between concentrations associated with toxicity (as low as 9 pg/ml) and the accepted therapeutic range (5-20 pg/ml). Most patients with toxicity had theophylline levels within the therapeutic range. 3 For the same dose of aminophylline there was sevenfold variation between patients in plasma theophylline, with higher conentrations in non-smokers, infrequent alcohol users, older patients, those with left ventricular failure and those with lower serum transaminases. These variables could not be separated completely because of the small number of observations. 4 A nomogram for aminophylline dosage or monitoring of serum theophylline levels would have prevented little of the toxicity observed in these patients, although these measures would ensure that therapeutic concentrations were attained, and might prevent life-threatening toxicity.

Prediction of maintenance oral theophylline dosage using single oral doses in patients with obstructive airways disease.

“…It is generally accepted that optimal effect is achieved within the 'therapeutic' range of 10-20 ,ug/ml, but dose selection in the individual patient to ensure concentrations within this range is difficult because wide inter-individual variation in the elimination half-life of the drug results in a four-fold variation in drug levels achieved on a fixed dose (Jenne et al, 1972). Furthermore, the advent of toxicity may occur at drug concentrations within the therapeutic range in some patients (Ramsay et al, 1980) although adverse symptoms are less common when plasma levels remain below 15 ,ug/ml (Jacobs et al, 1976). For these reasons, the minimum recommended dose is frequently prescribed by clinicians and because of practical difficulties, further adjustment based on monitoring plasma concentrations may be neglected (McDevitt et al, 1979).…”