[The potential clinical significance of the isoniazid acetylator phenotype in the treatment of pulmonary tuberculosis].

The most important factor determining the speed with which isoniazid is eliminated from the body is the rate of its acetylation in the liver. There are large differences between individuals in the rates at which isoniazid is acetylated. Over 98% of subjects can be clearly characterized as being either rapid of slow acetylators. Among the many satisfactory procedures for determining the acetylator phenotype of subjects, the simple sulphamethazine method is probably the most convenient. The proportions of rapid acetylators among different populations vary from about 40% among those of European and South Indian descent to over 85% among Japanese and Eskimos. The isoniazid acetylator phenotype of tuberculosis patients treated with isoniazid-containing regimens is without prognostic significance when treatment is given daily and only of doubtful importance when weak twice-weekly regimens are employed. However if treatment is given on a once-weekly basis, the response of rapid acetylators is generally much less satisfactory than that of slow acetylators. Since isoniazid is eliminated from the body predominantly by metabolism its clearance is not greatly diminished in the event of renal failure. As a consequence there are no grounds for reducing the dosage of isoniazid given to patients with impaired renal function. The incidence of the commonly encountered asymptomatic increases in serum transaminases associated with isoniazid treatment is similar in rapid and slow acetylators. Clinically important hepatic toxicity manifested by jaundice only occurs in 1-2% of patients treated with isoniazid-containing regimens. Despite earlier suggestions to the contrary, it is no more common in rapid than among slow acetylators. Since all patients can be treated effectively and safely with standard isoniazid dosages, determining patients' isoniazid serum/plasma levels or acetylator phenotype is hardly ever worthwhile. By contrast, since poor patient compliance is a major cause of therapeutic failure, monitoring the regularity with which patients self-administer their prescribed isoniazid treatment using simple urine-test methods can be of considerable value.