Rifampicin And Rifabutin Pharmacokinetics Mechanism Study

Both rifampin and rifabutin are rifamycins derivatives. They were used for the treatment of pulmonary tuberculosis, leprosy, Mycobacterium complex avium (MAC) and other Mycobacterium diseases. Often patients are taking multiple concurrent medications with rifampin or rifabutin in long term regimens.Much evidence has suggested that both drugs can induce the metabolism of many hepatically metabolized drugs such as anticoagulant agents, oral contraceptives, cyclosporine, digitoxin and verapamil. More interestingly, both drugs can also induce their own metabolism following repeated dosing. These will led to reduced therapeutic response, even therapeutic failure, drug tolerance or toxic reactions when rifampin or rifabutin is added to or discontinued from other medication regimens.It's very important to clarify the pharmacokinetic mechanism(s) of these two drugs. Thus, a series of experiments have been done in this paper and try to explore the induction and autoinduction properties of these two drugs.In autoinduction experiments, antipyrine kinetic and absorption studies using liver perfusion technique, antipyrine system pharmacokinetics and closed intestine loop show no significant changes after repeated exposure to rifampin. This result indicated that the pathway of autoinduction of rifampin is different from that of antipyrine. Meanwhile, there was no significant changes for...