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%.
Subject(s)
Acetylation , Acetyltransferases/genetics , Administration, Oral , Body Surface Area , Body Weight , Child , Child, Preschool , Dose-Response Relationship, Drug , Humans , Isoniazid/administration & dosage , Phenotype , Saliva/analysisABSTRACT
Self-induction of rifampicin metabolism during daily and intermittent chemotherapy was studied by monitoring the changes in the serum half-life of the drug over a 4-week period in patients with pulmonary tuberculosis. Rifampicin 450 mg was administered to 8 patients who received treatment daily, 7 on thrice-weekly and 7 others on twice-weekly treatment. Serum half-life was computed from concentrations of the drug determined at 3, 4 1/2 and 6 hours after drug administration, on admission and at 1, 2 and 4 weeks after start of treatment. In the daily series, the mean serum half-life decreased from 4.9 hours on admission to 3.6 hours at 1 week (P = 0.02), and treatment beyond this had no further effect. In the thrice-weekly series, maximal induction was observed at the 2nd week, the mean values on admission and at 2 weeks being 5.8 and 3.7 hours, respectively (P less than 0.01). In the twice-weekly series, maximal induction was observed only at the 4th week, the mean values on admission and at 4 weeks being 4.9 and 3.7 hours, respectively (P less than 0.01). Serum activity of gamma glutamyl transferase was not found to be a suitable in vivo marker to monitor induction of the hepatic microsomal enzymes as no significant changes were observed in the activity of this enzyme in any of the 3 series during the 4-week period.