Study On Pharmacokinetics Of Rifampicin And Isoniazid Administered In Combination And Bioavailability Of The Compound Preparations

Rifampicin and Isoniazid are the most effective and commonly used drugs in antituberculous chemotherapy. In clinic, RIF is usually administered in combination with Iso. Both of the two drugs are metabolized in hepatic. RFP is the inducer of hepatic cytochrome P-450 and metabolized by tuoyixianhua . INH is the inhibitor of hepatic cytochrome P-450 and metabolized by acetylation. It has been reported that the inducible RFP could accelerate the acetylation of INH, as results, the pharmacokinetics of INH would change, the concentration of Aclso in hepatic increase greatly and hepatic impairment even toxic hepatitis would be observed. There are papers reporting that when the two drugs administered in combination, the pharmacokinetic parameters (Ti/2,Cmax,AUC) were the same as those when administrated individually. Administration of the two drugs in combination has called for attention of of doctors and pharmacists. With the study going deep, more and more papers about drug interaction in vivo have emerged with various conclusions, the terms consisted of the change of pharmaceutics, the effecton drug resistance, the reinforcemen and reduction of the efficiency and Hepatotoxicity and so on. So it is necessary and of great importance to carry on further research. In this study, the effect on pharmacokinetics of the two drugs administered in combination was investigated by animal tests, and this can offer valuable reference for clinic therapy.The study consisted of two sections, in the first section, cross-over randomized design (four periods, two preparations) was employed, six healthy dogs were divided into two groups at random. One group was supplied with INK or RFP individually, the other was supplied with INK and RFP in combination, then the pharmacokinetic parameters were compared. The results showed that no bad effect occurred when the two drugs were administered in combination, and there were no significant difference in the pharmacokinetic parameters(Ti/2, Craax, AUC) between the two regimes of administration , the concentration-time curves of them were similar. The outcome suggested that the two drugs can be made in compound preparation to improve the patients' compliance and enhance curative effect of the two drugs.In the second section, 3X3 (three preparations and three cycles) Lading design was employed, imported Rifinah was taken as reference, study on the pharmacokinetics and relative bioavailability of domestic tablets and capsules of RFP and INH was performed to evaluate whether the three preparations were bioequivalent. It is reported that the crystal structure of RFP would be changed if made in tablet, and the bioavailability of RFP would experiencecorresponding change. In this study, the pharmacokinetic parameters of tablet were compared with those of capule. The results indicated that the quality of combined preparation can be guaranteed if the condition of production is good.