PHARMACOKINETICS OF FDC: RIFAMPIN AND ISONIAZID IN CHILDREN WITH PULMONARY TUBERCULOSIS
Aim. For tuberculosis with confirmed or suspected drug convenience of the pathogen, first-line anti-tuberculosis drugs are used: isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), as well as more combined for use can be combined with fixed doses (FDC), especially in childhood. The effectiveness of chemotherapy is influenced by many factors, including the bioavailability of the drugs. Purpose of the study. To study the features of the pharmacokinetics of rifampicin and isoniazid as part of a fixed dose combination preparation (H 150 mg + Z 375 mg + R 150 mg) for the treatment of drug-sensitive tuberculosis in children. Materials and methods. A comparative cohort study of the pharmacokinetics of rifampicin and isoniazid (the most active anti-tuberculosis drugs for the treatment of drug-sensitive tuberculosis) in the form of monopreparations and in the composition of FDC (H 150 mg + Z 375 mg + 150 mg R) was carried out. The study included 22 patients with newly diagnosed respiratory tuberculosis at the age from 2 to 17 years inclusive. All patients are treated according to the first (I) or third (III) chemotherapy regimens. Patients were conditionally divided into the main (FDC treatment) and control (mono-drug treatment) groups. Venous blood sampling (4 ml) for pharmacokinetic analysis of rifampicin derivatives, as well as 2, 4, 24 hours after taking the drugs. Conclusion. The fixed dose combination drug showed less variation in observed pharmacokinetic parameters. This allows them to be more accurately tracked and, in the long term, presumably oriented, appropriate to evaluate the factors influencing the manifestation of toxicity and safety, as well as the efficacy factors influencing factors such as the bioavailability of drugs, heterogeneity of fermenting systems of biotransformation agents.