Metronidazole and Tinidazole pharmacokinetics

Metronidazole and tinidazole are effective orally and distributed widely to tissues. The half-life of metronidazole is 6–8h, and that of tinidazole 12–14 h. Elimination of the drugs requires hepatic metabolism. For the treatment of amebiasis, metronidazole is usually administered with a luminal amebicide, such as iodoquinol or paromomycin. This combination provides cure rates of greater than 90 percent. Metronidazole distributes well throughout body tissues and fluids. Therapeutic levels can be found in vaginal and seminal fluids, saliva, breast milk, and cerebrospinal fluid (CSF). Metabolism of the drug depends on hepatic oxidation of the metronidazole side chain by mixed-function oxidase, followed by glucuronylation. Therefore, concomitant treatment with inducers of this enzymatic system, such as phenobarbital, enhances the rate of metabolism. Conversely, those drugs that inhibit this system, such as cimetidine, prolong the plasma half-life of metronidazole. The drug accumulates in patients with severe hepatic disease. The parent drug and its metabolites are excreted in the urine.