rifampin and piperine

The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. To overcome these concerns a new boosted formulation of Rifampicin (Risorine) with bio-enhancer Piperine was developed. Piperine has been found to increase bioavailability of several drugs including Amoxicillin, Cefotaxime, Theophylline and Propranolol. Risorine is a fixed dose combination that contains Rifampicin 200 mg + Isoniazid 300 mg + Piperine 10 mg.. The aim of the present study was to validate the therapeutic efficacy and tolerability of Risorine formulation containing regimen with a conventional regimen in the management of patients with newly diagnosed pulmonary tuberculosis.. Total 216 patients with sputum positive and treatment naïve pulmonary tuberculosis were enrolled in the study after fulfillment of inclusion / exclusion criteria. These patients were randomized to receive either a conventional anti-TB therapy (n = 117) or a similar regimen containing Risorine (n = 99) for 6 months. During the study period, symptomatic improvement, sputum conversion and radiological improvement were monitored at regular intervals.. Of the 216 enrolled patients, 75% in the Risorine group and 79% in the control group completed the study. At 4 weeks the sputum conversion rate was significantly superior in Risorine group (93%) than the control group (84%), which was consistence throughout the study. Cure rate at the end of 24 weeks, was higher in Risorine group (92%) than in the control group (82%). Elevation of liver enzymes were observed in 3 patients in the Risorine group and in 9 patients in control group.. Risorine, a novel formulation of low dose Rifampicin (200 mg), a bio enhancer Piperine (10 mg) and standard dose Isoniazid (300 mg) when given along with Ethambutol and Pyrazinamide was comparable in efficacy with standard WHO therapy using conventional formulation. Risorine provides more Rifampicin in blood compare to GI tract as well as maintaining higher blood levels on chronic therapy compared to conventional Rifampicin with better safety profile. Risorine gives higher sputum conversion rate during the Intensive Phase which is maintained till the end of study. Further a trend was also noticed towards better tolerability with newer formulation, Risorine. H = Isoniazid, R = Rifampicin, Z = Pyrazinamide and E = Ethambutol.

Topics: Adult; Alkaloids; Antibiotics, Antitubercular; Benzodioxoles; Drug Combinations; Female; Humans; Isoniazid; Male; Piperidines; Polyunsaturated Alkamides; Rifampin; Sputum; Tuberculosis, Pulmonary

The activity of rifampin (RIF) and piperine was evaluated at the relative transcript levels of 12 efflux pumps (EPs), and an additional mechanism was proposed to be behind the synergic interactions of piperine plus RIF in

Topics: Alkaloids; Antineoplastic Agents; Benzodioxoles; Binding Sites; DNA-Directed RNA Polymerases; Drug Synergism; Drug Therapy, Combination; Molecular Docking Simulation; Mycobacterium tuberculosis; Piperidines; Polyunsaturated Alkamides; Reverse Transcriptase Polymerase Chain Reaction; Rifampin

High performance liquid chromatography is an integral analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect any drug-related impurities that may be introduced during synthesis.. A simple, economic, selective, precise, and stability-indicating HPLC method has been developed and validated for analysis of Rifampicin (RIFA) and Piperine (PIPE) in bulk drug and in the formulation.. Reversed-phase chromatography was performed on a C18 column with Buffer (Potassium Dihydrogen Orthophosphate) pH 6.5 and Acetonitrile, 30:70), (%, v/v), as mobile phase at a flow rate of 1 mL min-1.. The detection was performed at 341 nm and sharp peaks were obtained for RIFA and PIPE at retention time of 3.3 ± 0.01 min and 5.9 ± 0.01 min, respectively. The detection limits were found to be 2.385 ng/ml and 0.107 ng/ml and quantification limits were found to be 7.228ng/ml and 0.325ng/ml for RIFA and PIPE, respectively. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines.. Stress study was performed on RIFA and PIPE and it was found that these degraded sufficiently in all applied chemical and physical conditions. Thus, the developed RP-HPLC method was found to be suitable for the determination of both the drugs in bulk as well as stability samples of capsule containing various excipients.

Topics: Alkaloids; Benzodioxoles; Capsules; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Drug Stability; Hydrolysis; Limit of Detection; Piperidines; Polyunsaturated Alkamides; Rifampin

To study the efficacy and tolerability of Risorine Capsule (A fixed dose combination of Rifampicin 200 mg + INH 300 mg + Piperine 10 mg) therapy in the treatment of drug-susceptible pulmonary tuberculosis patients who developed GI intolerance with standard WHO anti TB regimen.. 33 patients with pulmonary tuberculosis were treated with one Risorine kit, daily consisting of one capsule of Risorine, one tablet of ethambutol (800 mg) and two tablets of Pyrazinamide 750 mg each, for first two months of therapy. All the patients received one capsule of Risorine daily for next four months. Symptomatic improvement, Sputum conversion and radiological improvement were monitored at regular intervals.. Out of 27 patients who were sputum positive at baseline, 24 patients became sputum negative during the first two months of treatment. Out remaining three patients, one became sputum negative at the end of third month of treatment and the other two became sputum negative at the end of sixth month of treatment. Out of 33 patients, only two patients developed mild nausea, which subsided spontaneously. One patient who was HIV positive, developed hepatitis.. Risorine, a novel formulation of rifampicin 200 mg with bioenhancer piperine 10mg, is found to be highly effective and well tolerated in the treatment of drug - susceptible pulmonary tuberculosis.

Topics: Adult; Alkaloids; Antitubercular Agents; Benzodioxoles; Cytochrome P-450 Enzyme Inhibitors; Drug Combinations; Ethambutol; Female; Humans; Isoniazid; Male; Middle Aged; Pilot Projects; Piperidines; Polyunsaturated Alkamides; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary; Young Adult

Piperine a trans-trans isomer of 1-piperoyl-piperidine was evaluated for its immunomodulatory activity to enhance the efficacy of rifampicin in a murine model of Mycobacterium tuberculosis infection. In-vitro immunomodulation of piperine was tested on mouse splenocytes for lymphocyte proliferation, cytokine production and macrophage activation. Protective efficacy of piperine was tested in a mice infection model of M. tuberculosis for the activation of Th-1 response and synergistic combination efficacy with rifampicin. Murine splenocytes exposed to piperine exhibited proliferation of T and B cell, increased Th-1 cytokines and enhanced macrophage activation. Piperine (1 mg/kg) in mice infected with M. tuberculosis activated the differentiation of T cells into Th-1 sub-population (CD4+ / CD8+ subsets). There was an increase in secretion of Th-1 cytokines (IFN-γ and IL-2) by these cells. The qRT-PCR studies revealed corresponding increases in the mRNA transcripts of IFN-γ and IL-2 in the infected lung tissues. Combination of piperine and rifampicin (1 mg/kg) exhibited better efficacy of and resulted in additional 1.4 to 0.8 log reduction in lung cfu as compared to rifampicin alone. The up-regulation of Th1 immunity by piperine can be synergistically combined with rifampicin to improve its therapeutic efficacy in immune-compromised TB patients.

Topics: Alkaloids; Animals; Antitubercular Agents; Benzodioxoles; Cell Proliferation; Cells, Cultured; Colony Count, Microbial; Drug Combinations; Drug Evaluation, Preclinical; Immunophenotyping; Interferon-gamma; Interleukin-2; Lung; Lymphocyte Activation; Macrophage Activation; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Nitric Oxide; Piperidines; Polyunsaturated Alkamides; Rifampin; RNA, Messenger; Spleen; Th1 Cells; Tuberculosis

To evaluate the role of piperine as an inhibitor of Rv1258c of Mycobacterium tuberculosis.. Rifampicin, in combination with piperine, was tested against M. tuberculosis H37Rv and rifampicin-resistant (rif(r)) M. tuberculosis. A laboratory-generated rifampicin-resistant mutant (rif(r)) of M. tuberculosis was tested for drug susceptibility and the expression level of the putative efflux protein (Rv1258c) by real-time PCR. The three-dimensional (3D) structure of Rv1258c was also predicted using an in silico approach.. In the present study, rifampicin in combination with piperine, a trans-trans isomer of 1-piperoyl-piperidine, reduced the MIC and mutation prevention concentration (MPC) of rifampicin for M. tuberculosis H37Rv, including multidrug-resistant (MDR) M. tuberculosis and clinical isolates. Moreover, piperine effectively enhanced the bactericidal activity of rifampicin in time-kill studies and also significantly extended its post-antibiotic effect (PAE). In the presence of rifampicin, M. tuberculosis rif(r) showed a 3.6-fold overexpression of Rv1258c. The 3D structure of Rv1258c, using in silico modelling, was analysed to elucidate the binding of piperine to the active site.. The results of this study are suggestive of piperine's involvement in the inhibition of clinically overexpressed mycobacterial putative efflux protein (Rv1258c). Piperine may be useful in augmenting the antimycobacterial activity of rifampicin in a clinical setting.

Topics: Alkaloids; Antitubercular Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Benzodioxoles; Drug Synergism; Enzyme Inhibitors; Gene Expression Profiling; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Piperidines; Polymerase Chain Reaction; Polyunsaturated Alkamides; Protein Structure, Tertiary; Rifampin

Topics: Adult; Alkaloids; Benzodioxoles; Biological Availability; Female; Humans; Male; Middle Aged; Piperidines; Polyunsaturated Alkamides; Rifampin; Tuberculosis, Pulmonary