Study on 12 healthy volunteers using 2 types of medication: rifampicin, isoniazid, and pyrazinamid standard separate tablets and in fixed dose combination of rifampicin + isoniazid + pyrazinamid (3- FDC). Results: rifampicin is one of essential anti-tuberculosis drugs that have most advantages of pharmacodynamics on both intra- and extra-cellular bacteria. Cmax (maximum concentration in plasma) and AUC 0-∞ (Area Under the Concentration-Time Curve) of rifampicin in 3- FDC is lower than that in standard separate tablet, Tmax (Time to Maximum Plasma Concentration) of rifampicin in 3- FDC is more slowly than in standard separate tablet. These findings showed that the bioavailability of rifampicin in FDC tablet that was using in treating tuberculosis is much lower than in standard separate tablet.
Biological Availability ; Rifampin ; Tablets

A HPLC method has been used to quantify plasma rifampicin and isoniazid and pyrazinamide simultaneously. Extraction of rifampicin in plasma samples was done as follows: mix 1ml of plasma containing rifampicin and 1.5 ml acetonitril on a vortex mixer for 1 minute prior to centrifugation at 3500 rpm for 30 minutes. The organic layer was filtered through 0.45m filter membrane and then 30l of this solution was injected into the HPLC system. The chromatographic conditions were as follows: in stationary phase: column: Apollo Alltech RP18 (250 x 4.6 mm; 5 m); in mobile phase: methanol - phosphate buffet solution containing 0.02M potassium dihydrogen phosphate adjusted to pH 4.5 by adding phosphoric acid (65: 35); Flow rate: 1.0 ml/min and UV detector: 254 nm
Chromatography, High Pressure Liquid ; lasma ; Pyrazinamide ; Isoniazid ; Rifampin

Background: Rifampicin, isoniazid, and pyrazinamide are oral essential anti-tuberculosis drugs on single or combined preparations. Worldwide research has shown that the plasma concentration of anti-tuberculosis drugs with daily therapeutic doses were seen significant lower than permitted in tuberculosis patients, especially for rifampicin and isoniazid. Objective: To investigate plasma concentration of rifampicin, isoniazid, and pyrazinamide in pulmonary tuberculosis and pleural tuberculosis patients. Methods: Determine plasma concentration of rifampicin, isoniazid, and pyrazinamide at 2 hours after administration in 168 tuberculosis patients by the HPLC method. Identify prevalence of low plasma concentrations of anti-tuberculosis drugs. Results: There was a wide range of plasma concentration of rifampicin, isoniazid, and pyrazinamide in the tuberculosis patients. The mean plasma concentration of rifampicin was 6.13 \xb1 4.66 microgram/ml, of isoniazid was 2.99 \xb1 1.94 microgram/ml, pyrazinamide was 38.98 \xb1 18.39 microgram/ml. There was no significant differences in the plasma concentration of rifampicin, isoniazid, and pyrazinamide in groups of pulmonary tuberculosis and pleural tuberculosis patients. Percentage of patients with plasma concentration below therapeutic concentration was 76.83% of rifampicin, 51.85% of isoniazid, 10.13% of pyrazinamide. There were 12.03% of patients who had pyrazinamide concentration higher than the therapeutic range. Conclusions: There was a wide range of plasma concentration in rifampicin, isoniazid, and pyrazinamide of tuberculosis patients. Low plasma concentration of rifampicin and isoniazid are common. It may be necessary to optimize the drug dose by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.
tuberculosis ; rifampicin ; isoniazid ; pyrazinamide

Comparative bioavailability study of rifampicin from 2-FDC and 3- FDC with standard separate tablets at the same dose level was conducted in 12 healthy volunteers. The study was designed as a cross-over experiment with a washout period of 1 week. Bioavailability of rifampicin was estimated by plasma concentration of rifampicin from Oh to 24h after dosed. Plasma rifampicin concentration was determined by HPLC method. The results revealed that: Cmax and AVC for rifampicin in 2-FDC and 3FDC formulation were lower (but Tmax were higher) than the standard separate formulations. It was concluded that FDC tablets are of poor relative bioavailabity of rifampicin. The implication for National Tuberculosis Programme is extremely serious and warrants urgent attention
Tuberculosis ; Pharmaceutical Preparations ; Therapeutics

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, an extract of the dried whole plants of Euphorbia supina Rafin was found to significantly inhibit sEH activity in vitro. Phytochemical investigation of E. supina resulted in isolation of 17 compounds (1 - 17), including triterpenes (1 - 4), phenolic compounds (5 - 8), and flavonoid derivatives (9 - 17). The structures of the isolated compounds were established mainly by extensive analysis of the 1D and 2D NMR, and MS data. All of the isolated compounds were evaluated for their sEH inhibitory activity. Among the isolated phenolic compounds, 8 was identified as a significant inhibitor of sEH, with an IC50 value of 15.4 +/- 1.3 microM. Additionally, a kinetic analysis of isolated compounds (2, 5, 8 - 11, 13, and 17) indicated that the inhibitory effects of flavonoid derivatives 10 and 11 were of mixed-type, with inhibitory constants (Ki) ranging from 3.6 +/- 0.8 to 21.8 +/- 1.0 microM, whereas compounds 2, 5, 8, 9, 13, and 17 were non-competitive inhibitors with inhibition Ki values ranging from 3.3 +/- 0.2 to 39.5 +/- 0.0 microM.
Euphorbia* ; Euphorbiaceae ; Inhibitory Concentration 50 ; Phenol ; Triterpenes

Phytochemical investigation of Kandelia candel resulted in the isolation of six triterpenes (1 - 5) and two glyceryl glycosides (6 and 7) and their structures were determined by comparing the spectroscopic data with those of reported values. In present study, we described the inhibitory effects of fractions and isolated compounds from K. candel on pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-alpha) production in lipopolysaccharide (LPS) stimulated bone marrow-derived dendritic cells (BMDCs). Results indicated that compounds 3, 6, and 7 showed potent inhibition on IL-6 production (IC50 values at less than 0.5 microM, respectively). Meanwhile, compounds 6 and 7 exhibited strong inhibitory effects on the production of TNF-alpha (IC50 values of 1.7 +/- 0.1 and 5.5 +/- 0.2 microM). Compounds 1 and 3 were also showed the inhibitory effects on IL-12 p40 production (IC50 values of 8.9 +/- 0.4 and 3.3 +/- 0.1 microM, respectively).
Cytokines ; Dendritic Cells ; Glycosides* ; Interleukin-12 ; Interleukin-6 ; Rhizophoraceae* ; Triterpenes* ; Tumor Necrosis Factor-alpha