THEOPHYLLINE DISPOSITION IN ACUTELY ILL HOSPITALIZED-PATIENTS - EFFECT OF SMOKING, HEART-FAILURE, SEVERE AIRWAY-OBSTRUCTION, AND PNEUMONIA

Abstract

Theophylline disposition (clearance, volume of distribution and half-life) was measured in 31 normal volunteers and 26 acutely ill patients with airway obstruction within 24 h of hospital admission and again when i.v. aminophylline was discontinued 2-10 days later. Sex, age, race, the diagnosis of asthma and the diagnosis of chronic bronchitis were not significantly correlated with clearance. Clearance was significantly increased in smokers and significantly decreased in patients with congestive heart failure, pneumonia and severe bronchial obstruction. The volume of distribution was not correlated with these variables. Within 24 h of admission, the mean clearance in the patients without congestive heart failure or pneumonia was 44.5 ml/h per kg of body wt, 40% less than the value on which the 0.9 mg/kg per h dosage is based. The unexplained interindividual clearance variability was significantly higher among patients than control subjects; intraindividual variability in clearance was not different in these 2 groups after the effects of smoking, congestive heart failure, etc., was corrected. Large variability makes the plasma theophylline concentration resulting from any dosage relatively uncertain. Recommendations were made concerning theophylline dosage computation, and the clinical circumstances calling for determination of plasma theophylline concentrations.