Effect of disease states on theophylline elimination

Abstract

Host factors play an important role in the dosing requirements of theophylline. Theophylline metabolism and clearance depend principally on liver cell function rather than on hepatic flow. The effects of acute hypoxemia require more study; however, patients with chronic obstructive pulmonary disease who have chronic hypoxemia appear to have some impairment of clearance. Clearance is variably and sometimes drastically reduced in patients with liver disease and heart failure, and is reduced by some viral infections. It is not impaired by renal failure. Current split-virus vaccine mixtures do not appear to affect clearance. Clearance is increased in patients with cystic fibrosis and hyperthyroidism. The depressed clearance seen in the severely ill patients who require intensive care improves with improvement in the patient's condition, but the individual factors involved have not been identified. An area requiring more study is the effect of pH on the apparent distribution volume for theophylline. In the presence of liver disease, heart failure, or serious illness, caution must be applied in theophylline dosing, with frequent monitoring of serum levels. Stable patients also warrant an initially conservative dose until serum levels are obtained to guide further dose adjustments.