Induction of rifampicin metabolism during treatment of tuberculous patients with daily and fully intermittent regimens containing the drug.
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.
Immanuel
C
C
Jayasankar
K
K
Narayana
A S
AS
Santha
T
T
Sundaram
V
V
Sarma
G R
GR
D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004790:Enzyme Induction; D004977:Ethambutol / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008862:Microsomes, Liver / Q000201:enzymology; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy*; D005723:gamma-Glutamyltransferase / Q000097:blood
D011718:Pyrazinamide; D004977:Ethambutol; D005723:gamma-Glutamyltransferase; D007538:Isoniazid; D012293:Rifampin