Serum concentrations of rifampicin and isoniazid in tuberculosis.
Ninety-four patients, 1-13 years of age suffering from different types of tuberculosis were investigated for serum rifampicin (RIF) and isoniazid (INH) concentrations using microbiological and fluorimetric methods, respectively. Of these, 64 (68.1%) had pulmonary primary complex (PPC); 20 (21.3%) progressive primary disease (PPD) and 10 (10.6%) tuberculous meningitis (TBM). Patients with PPC, PPD and TBM were given two-drug (6HR), three drug (2HRZ, 4HR) and four drug (2SHRZ, 4HRE, 3HE) regimens, respectively. RIF and INH were administered in a dose of 12 and 10 mg/kg/day, respectively. After 10-12 days of continuous therapy, their serum concentrations were estimated at 0, 2, 4, 6, 8 hours for RIF and 0, 1, 3, 5, 7 hours for INH. For RIF, the time to achieve maximum concentrations (Tmax) was 2 hours, range of mean of maximum concentration (Cmax) 3.38 to 3.88 micrograms/ml, terminal half life elimination (T1/2) 3.03 to 3.81 hours and area under serum concentration curve (AUC) 0-8 hours 24.7 to 28.3 micrograms/ml hours in different forms of tuberculosis. INH had a Tmax of 1 h, Cmax 4.38 to 8.17 micrograms/ml, T1/2 4.0 to 4.98 hours and AUC 0-7 hours 34.1 to 57.5 micrograms/ml hours. The concentrations achieved at 7-8 hours with these dosages were much above those required for therapeutic efficacy (minimum inhibitory concentration), being 50 to 250 times for RIF and 35-60 times for INH. We recommend pharmacokinetic studies with lower doses of RIF and INH for less toxic, equally effective and cheaper antitubercular chemotherapy.
Seth
V
V
Department of Pediatric Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
Beotra
A
A
Seth
S D
SD
Semwal
O P
OP
Kabra
S
S
Jain
Y
Y
Mukhopadhya
S
S
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood*; D013997:Time Factors; D014390:Tuberculosis, Meningeal / Q000097:blood* / Q000188:drug therapy; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy
D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin