Influence of cigarette smoking on drug metabolism in man.

The pervasiveness of tobacco use in our society and the frequency of altered disposition of many common therapeutic and recreational drugs in smokers makes it apparent that the smoking habit should be considered as one of the primary sources of drug interactions in man. Each scientific report dealing with drug disposition should list the smoking status of the subjects studied as smoking should be included as a basic characteristic of each subject along with age, race, body weight, and presence and type of disease. Most of the experimental work in human and animal systems indicates that the dominant effect of smoking is enhanced disposition caused by induction of hepatic microsomal enzymes. The primary causal agents are probably the polynuclear aromatic hydrocarbons which are potent and persistent in tissues. There are numerous examples of both an increased metabolism rate and absence of an effect of smoking on drug disposition in man. This selectivity is consistent with the known inductive effects of P-448 stimulators in animal systems. Studies with theophylline have demonstrated that both tobacco and marijuana markedly alter its clearance in man. However, smoking is only one of numerous factors which can perturb hepatic biotransformation as patient surveillance studies show that age and cardiac and liver disease may be of greater importance in actual patients undergoing therapy.