Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. II. Two-month, daily administration study.
The time course of the plasma concentrations of isoniazid, rifampin, and pyrazinamide was assessed in a group of 13 patients with lung tuberculosis treated over a period of 2 months on a continuous daily basis with a fixed triple combination of the same drugs. The blood kinetics of the three antituberculosis drugs were determined on Days 1, 15, 30, and 60 of treatment. The triple combination employed in this study contained 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet, the number of tablets ranging from four to seven per day according to the body weight of the patients. Almost superimposable plasma concentration curves for isoniazid were observed during the 4 days of the study. For rifampin, a fall in the plasma concentrations at the time intervals after the peak was observed comparing the data on Day 1 with those on Days 15, 30, and 60, which did not differ from each other. This finding is thought to be due to the well-known phenomenon of self-induction, which leads to an increased rate of disposal of the antibiotic from the blood compartment within the first and second weeks of continuous treatment. For pyrazinamide, an equilibrium in the opposite sense as that of rifampin seemed to take place within the 2 months of the study. Because of the relatively high plasma levels observed 24 h after each administration, an increase in plasma concentrations with respect to those observed on Day 1 was found on Days 15, 30, and 60, the levels on these days no differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)
Acocella
G
G
Reference Center for Chemotherapy of Mycobacterial Diseases, Istituto Forlanini, Pavia, Italy.
Nonis
A
A
Perna
G
G
Patane
E
E
Gialdroni-Grassi
G
G
Grassi
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011718:Pyrazinamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000995:Antitubercular Agents; D004338:Drug Combinations; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin