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)
Seth
V
V
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
Seth
S D
SD
Beotra
A
A
Semwal
O P
OP
D'monty
V
V
Mukhopadhya
S
S
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000097:blood* / Q000627:therapeutic use* / Q000652:urine*; D008297:Male; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
D007538:Isoniazid; D012293:Rifampin