[Pharmacodynamics and pharmacokinetics of domestic fixed-dose combination of antituberculosis drugs].
OBJECTIVE To study the pharmacodynamics and pharmacokinetics of domestic fixed-dose of antituberculosis drugs  and to evaluate its quality and activity against Mycobacterium tuberculosis both in vitro and in vivo. METHODS The MIC was determined by the tube doubling dilution method, and the effect of the drugs was assessed by half survival time of the mice. A single oral dose of domestic and imported fixed-dose combination of antituberculosis drugs was given to healthy volunteers, and the drug concentration in serum was determined by HPLC. The pharmacokinetic parameters and the relative bioavailability were calculated. RESULTS The MIC of each composition in the compound (INH, RFP, PZA) against  Mycobacterium tuberculosis was lower than that of each composition used by single-dose. In a murine tuberculosis model, the antituberculosis activity of this compound drug was superior to that of each agent used alone with the same dose. No significant difference was found as compared to the imported drug, Refater; The major pharmacokinetic parameters of the domestic and the imported drugs, t (1/2), C (max), AUC, and t(max), were not significantly different. Statistical analysis showed the two formulations were bioequivalent. CONCLUSION The three compositions in the combination had synergistic effect, and the domestic and the imported drugs were bioequivalent.
Department of Pharmacology,Beijing Institute of Tuberculosis and Thoracic Tumor, Beijing 101149, China.
Weijie
W
Zhao
Huiwen
H
Li
Lianshan
L
Duan
Guifang
G
Liang
Tongqun
T
Zhang
Yu
Y
Lu
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013810:Therapeutic Equivalency
D000995:Antitubercular Agents