Abstract
An intravenous fall-off technique for determining individual patterns of isoniazid metabolism is described. It utilizes a previously described, simple chemical method for the determination of free isoniazid. It is believed that the technique offers both clinical and investigative advantages over existing methods. Most of the patients studied to date fall into 2 groups, one with a mean half-life of 59 min. (45 to 80), and the other with a mean hall-life of 159 min. (140-180). The rate-dominating process is shown to be approximately first-order, and far from saturated in both groups. A group of patients with abnormal liver function was tested, and the results were suggestive of a slight delay in some of those with slower fall-offs. The delays would seem to be too small to be of any clinical importance. Circulatory congestive failure is seen to prolong the half-life. Extremely prolonged half-lives of 455 and 640 min. were recorded in one apparently normal patient. It can be calculated that during the intravenous test the slow-normal group has approximately 2 1/2 times the time-concentration drug exposure of the rapid group, and that this product is proportional to the half-life and the initial drug concentration.