Classification of children as slow or rapid acetylators based on concentrations of isoniazid in saliva following oral administration of body-weight and surface-area-related dosages of the drug.

ABSTRACT

The acetylator phenotype of 180 children aged 3-11 years was determined on the basis of isoniazid concentrations in saliva collected at 5 hours after oral administration of body-weight and surface-area-related dosages of the drug in a syrup form. Isoniazid 2.5 mg/kg was administered on one occasion and 75 mg/m2 surface-area on another, with an interval of 3 days between the occasions. A cross-over design was employed and the sequence was determined by random allocation. The distribution of the concentrations was bimodal with both procedures, indicating the presence of two groups namely, the slow and rapid acetylators. The criterion for a rapid acetylator was a concentration of 0.3 micrograms/ml or less by body-weight-related dosage and 0.4 micrograms/ml or less by that based on surface-area. Based on these criteria, 62% of the children were classified as slow acetylators and 38% as rapid acetylators by body-weight, and 59 and 41%, respectively by surface-area, and the findings were similar in children in the different age-groups. The agreement between the two procedures was 98%.