The clinical significance of the effects of cigarette smoking on drug disposition.

Cigarette smoking is one of a number of environmental factors that contribute to interindividual variations in response to an administered drug. Polycyclic aromatic hydrocarbons present in cigarette smoke induce hepatic aryl hydrocarbon hydroxylase and cytochrome P448 and increased levels of these enzymes are responsible for a higher metabolic clearance of drugs which are substrates for these enzymes. The clinical significance of this induction is greatest for those drugs with a low therapeutic index such as theophylline. In some cases a modification of the normal therapeutic dose is justified to maintain adequate control. The magnitude of the effect of cigarette smoking on the induction of hepatic metabolic activity has been linked with age for a number of drugs including theophylline, some benzodiazepines and propranolol. Generally, the inductive effect is smaller in the elderly but, as there is no direct correlation between chronological age and physiological age, it is imperative that age and smoking habits be treated as individual sources of intersubject variation in pharmacokinetics and that this be borne in mind in the evaluation of new drugs and the safe clinical use of existing ones.