Determination of Cmax and Tmax of Fixed-Dose Combination (FDC) of Anti-Tubercular Drugs by performing High-Performance Liquid Chromatography (HPLC)
Keywords:
Tuberculosis, Fixed-dose combination, TDM, HPLC, CmaxAbstract
Tuberculosis (TB) is a leading cause of mortality and morbidity around the world. Every year, more than 9 million individuals are diagnosed with active tuberculosis, and 1.6 million people die as a result of the illness. We, therefore, determined the pharmacokinetic parameter of Cmax and Tmax of the fixed-dose combination of anti-TB drugs in patients by performing TDM using High-Performance Liquid Chromatography (HPLC) using pharmacokinetic sampling. In 30 TB patients, plasma concentrations were determined just before and at 1, 2, 4, 8, 12, 16, and 24 h after observed drug intake to assess the peak plasma concentrations (Cmax) and Time to achieve peak plasma concentration (Tmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. The Cmax was below the reference range for isoniazid in 30 patients and rifampin in 24/30 patients. The Cmax for pyrazinamide and ethambutol was not below the reference range in any of the patients. Increasing the dose of isoniazid and rifampicin may simultaneously also increase the concentration of pyrazinamide and ethambutol, which is already in between the reference range. The desired therapeutic effect of isoniazid and rifampicin may not be produced in the patients. In FDC drugs, it is impossible to withdraw a single drug that produces a side-effect, ADR, and increasing or decreasing the dose of a single drug is not possible in this formulation. So, due to the above reasons and problems, suggesting using individual drugs in the tuberculosis treatment instead of a Fixed-Dose Combination (FDC).
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