DETERMINATION OF THE ISONIAZID INACTIVATOR PHENOTYPE

Abstract

There are two distinct patterns of isoniazid metabolism present in the human species. Some persons show a rapid fall in plasma isoniazid concentration following drug ingestion, while others show only a slow fall. An individual human subject has a consistent pattern. This pattern is genetically determined; the Mendelian dominant character of rapid inactivation is thought to be due to greater acetylation of the drug than occurs in the presence of the recessive character. The decline in plasma isoniazid concentration over 6 hours following drug ingestion has been shown to be exponential. The "half-life" of plasma isoniazid is a method of phenotyping, and it has been shown that this can be determined fairly accurately by 2 observations, the 1st at 2 hours, and the 2d at 6 hours following drug ingestion. Another method of determining the isoniazid inactivator phenotype is by determining the 6-hour plasma concentration only. When this is done by means of a chemical technique, the bimodality in the distribution of the values is rather clearer than when a microbiologic technique is used. When the same samples of blood are assayed by the chemical and microbiologic methods, then there is a strong positive correlation between the results. When the 128 subjects studied were classified for phenotype by the chemical technique, it was found that 39 of 78 white subjects and 26 of 50 U. S. Negro subjects were rapid inactivators. This suggests that the distribution of phenotypes is similar in these 2 ethnic groups.