Isoniazid is rapidly absorbed after oral administration, but at the same time taking the drug with food its absorption and bioavailability is reduced. After a single oral administration of 300 mg the maximum plasma concentration observed after 1-2 hours Connection with the plasma protein -. 0-10%. It penetrates into various tissues and body fluids, including bone and cerebrospinal fluid. Is acetylated and hydrolyzed in the liver. Acetylation – this is the main way of isoniazid metabolism. acetylation rate depends on the individual patient. Isoniazid metabolites have no antimicrobial activity. If abnormal liver function the half-life of isoniazid is prolonged. Within 24 hours, it is excreted in urine as metabolites clen, in an unmodified form – up to 12% during rapid acetylation and up to 27% in slow acetylation. In severe renal insufficiency in patients with slow acetylation possible drug accumulation.
Pyrazinamide is rapidly and almost completely absorbed from the gastrointestinal tract. It penetrates into various tissues and body fluids. After a single oral administration maximum plasma concentration observed after 1-2 hours, pirazinoevoy acid (the active metabolite.) – 4-5 hours Kintsentratsiya in the cerebrospinal fluid of 87-100% of the plasma concentration. Relationship to plasma proteins – 10-20%, pirazinoevoy acid – 31%. Pyrazinamide biotransformation in the liver, where under the influence of microsomal enzymes pirazinoevoy first hydrolyzed to the acid (which is an active metabolite) and then converted into inactive metabolite – 5 gidroksipirazinoevuyu acid. The half-life of pyrazinamide – about 9.5 hours pirazinoevoy acid -. About 12 hours In renal insufficiency, the time increased to 26 hours and 22 hours, respectively. The drug is excreted mainly in urine within 72 hours: about 3% – as unchanged drug, 33% – as pirazinoevoy acid and 36% – in the form of other metabolites.
All forms of tuberculosis, and the localization clen (treatment, including outpatient basis, chemoprophylaxis, preventive treatment).
Inside, the food, 5-10 mg / kg body weight (dosage Ftizopirama carried on isoniazid) once daily in the period of intensive therapy (3-4 months), then – in a day.Total course dose Ftizopirama for each patient is individual and depends on the nature of the disease, treatment effectiveness and tolerability.
Liver: possible violation of liver function, especially in patients with malnutrition or previous liver disease, as well as in the elderly. It is recommended to monitor the levels of ALT and AST in plasma and on a monthly basis to assess liver function. Isoniazid should be lifted only in those cases where the transaminase levels to more than 3 times the upper limit of normal, as is often noted asymptomatic transient increase in liver enzymes, which does not require discontinuation. With the development of acute or chronic hepatitis Isoniazid should be abolished, in the latter case it is impossible to resume therapy with isoniazid. Drinking alcohol during therapy with isoniazid can increase the risk of hepatitis.
From the gastrointestinal tract: nausea, vomiting, abdominal pain, diarrhea, exacerbation of peptic ulcer.
On the part of the central and peripheral nervous system: sometimes may develop peripheral neuropathy, particularly in elderly patients, pregnant women, patients with malnutrition, diabetic patients, and in patients with chronic liver disease, including alcoholic etiology. For clen the prevention of peripheral neuropathy it is recommended to take pyridoxine.
Other: allergic reactions, gynaecomastia, menorrhagia.