Isoniazid and acetylisoniazid kinetics in serum and urine in pulmonary primary complex with intermittent regimen.

Twenty patients, 1 through 13 years of age from Pediatric Tuberculosis Clinic of All India Institute of Medical Sciences, New Delhi, suffering from pulmonary primary complex (PPC) were investigated for serum and urine concentrations of isoniazid (INH) and acetylisoniazid (AcINH). Patients were put on an intermittent regimen - 2HR, 4H2R2, INH (H) was given in a dose of 10 mg/kg/day for first 2 months (the daily dose phase), followed by 20 mg/kg/dose in biweekly phase of regimen for rest of the 4 months, whereas, rifampicin (R) was given as 12 mg/kg in both daily as well as biweekly phases. In the biweekly phase of regimen, after 7 days of biweekly administration of drugs, INH and AcINH concentrations were estimated by HPLC at 0,1,3,5 and 7 hours in serum, and at 0-3, 3-6, 6-12 and 12-24 hour-intervals of drug administration in urine. Peak concentrations of INH and AcINH (Mean +/- SD) were 2.6 +/- 1.8 and 5.5 +/- 2.6 micrograms/ml in serum (Cmax), and 5.7 +/- 4.8 and 21.5 +/- 12.1 mg in urine, respectively. Time to achieve Cmax (Tmax), for INH and AcINH were 1 and 5 hours respectively while time of peak concentration in urine for INH was 3-6 hours and for AcINH 6-12 hours. The half-life (T1/2) of INH was 4.5 hours and area under serum-concentration time-curve (AUC0-7h) was 20.7 micrograms/ml/h (mean values). In biweekly phase (4H2R2) of regimen, just before administration of next dose, 0 hour (or 72 hours) concentration of INH was estimated at 0.47 +/- 0.3 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual evoked responses in tuberculous children on ethambutol therapy.

Visual evoked responses (VERs) were recorded in 47 children, aged 3-13 years with tuberculosis, treated with ethambutol (20 mg/kg/day) as a part of the antitubercular regimen. VERs were evoked by monocular whole field stimulation, the stimulus being provided by a black and white checker-board pattern reversed every 560 msec and recorded before the commencement, 2, 4, 6, 9 and 12 months of therapy and between 3 to 6 months after stopping the drug. In the first 6 months of therapy the mean values of latency ranged from 92.8 to 101.3 msec in the 3 to less than 6 years age group and 88.5 to 100.3 msec in children 6-13 years of age. Between 6-12 months of therapy the mean values of latency were between 93.3 to 101.0 msec in the 3 to less than 6 years age group and 96.0 to 101.5 msec in the older group. Between 3-6 months after stopping therapy the means of latency ranged from 92 to 96 msec. The differences were not statistically significant at any point of time. Thus, children do not seem to be at greater risk for developing ethambutol inducted optic damage as compared to adults. Ethambutol in the above stated dose may, therefore, be recommended for inclusion in antitubercular chemotherapy in pediatrics without undue fear of subclinical toxicity.