Targeting ROS-AMPK pathway by multiaction Platinum(IV) prodrugs containing hypolipidemic drug bezafibrate.

Alterations in lipid metabolism, commonly disregarded in the past, have been accepted as a hallmark for cancer. Exploring cancer therapeutics that interrupt the lipid metabolic pathways by monotherapy or combination with conventional chemotherapy or immunotherapy is of great importance. Here we modified cisplatin with an FDA-approved hypolipidemic drug, bezafibrate (BEZ), via the well-established Pt(IV) strategy, affording two multi-functional Pt(IV) anticancer agents cis,cis,trans-[Pt(NH3)2Cl2(BEZ)(OH)] (CB) and cis,cis,trans-[Pt(NH3)2Cl2(BEZ)2] (CP) (BEZ = bezafibrate). The Pt(IV) prodrug CB exhibited an enhanced anticancer activity up to 187-fold greater than the clinical anticancer drug cisplatin. Both CB and CP had less toxicity to normal cells, showing higher efficacies and superior therapeutic indexes than cisplatin. Mechanism studies revealed that the bezafibrate-conjugated Pt(IV) complex CB, as a representative, could massively accumulate in A549 cells and genomic DNA, induce DNA damage, elevate intracellular ROS levels, perturb mitochondrial transmembrane potentials, activate the cellular metabolic sensor AMPK, and result in profound proliferation inhibition and apoptosis. Further cellular data also provided evidence that phosphorylation of AMPK, as a metabolic sensor, could suppress the downstream HMGB1, NF-κB, and VEGFA, which may contribute to the inhibition of angiogenesis and metastasis. Our study suggests that the antitumor action of CB and CP mechanistically distinct from the conventional platinum drugs and that functionalizing platinum-based agents with lipid-modulating agents may represent a novel practical strategy for cancer treatment.

Trace amounts of fenofibrate acid sensitize the photodegradation of bezafibrate in effluents: Mechanisms, degradation pathways, and toxicity evaluation.

Effluent organic matter (EfOM), which is composed of background natural organic matter (NOM), soluble microbial degradation products, and trace amounts of organic pollutants, can play an important role in the photodegradation of emerging pollutants in the effluent. In this study, the impact of organic pollutants, using fenofibrate acid (FNFA) as a representative, on the photodegradation of emerging contaminants, using bezafibrate (BZF) as a representative, in effluents was investigated. It is found that BZF undergo fast degradation in the presence of FNFA although BZF is recalcitrant to degradation under simulated sunlight irradiation. The promotional effect of FNFA is due to the generation of singlet oxygen (1O2) and hydrated electrons (e-aq). Based on the structures of the identified intermediates, 1O2 initiated oxidation and e-aq initiated reduction reactions were the main photodegradation pathways of BZF in the effluents. The toxicity of the main photodegradation intermediates for BZF and FNFA was higher than that of the parent compounds, and the acute toxicity increased during simulated sunlight irradiation. The results demonstrated that trace amounts of organic compounds in EfOM can play an important role in sensitizing the photodegradation of some emerging pollutants in the effluent.

Degradation of lipid regulators by the UV/chlorine process: Radical mechanisms, chlorine oxide radical (ClO•)-mediated transformation pathways and toxicity changes.

Degradation of three lipid regulators, i.e., gemfibrozil, bezafibrate and clofibric acid, by a UV/chlorine treatment was systematically investigated. The chlorine oxide radical (ClO•) played an important role in the degradation of gemfibrozil and bezafibrate with second-order rate constants of 4.2 (±0.3) × 108 M-1 s-1 and 3.6 (±0.1) × 107 M-1 s-1, respectively, whereas UV photolysis and the hydroxyl radical (HO•) mainly contributed to the degradation of clofibric acid. The first-order rate constants (k') for the degradation of gemfibrozil and bezafibrate increased linearly with increasing chlorine dosage, primarily due to the linear increase in the ClO• concentration. The k' values for gemfibrozil, bezafibrate, and clofibric acid degradation decreased with increasing pH from 5.0 to 8.4; however, the contribution of the reactive chlorine species (RCS) increased. Degradation of gemfibrozil and bezafibrate was enhanced in the presence of Br-, whereas it was inhibited in the presence of natural organic matter (NOM). The presence of ammonia at a chlorine: ammonia molar ratio of 1:1 resulted in decreases in the k' values for gemfibrozil and bezafibrate of 69.7% and 7%, respectively, but led to an increase in that for clofibric acid of 61.8%. Degradation of gemfibrozil by ClO• was initiated by hydroxylation and chlorine substitution on the benzene ring. Then, subsequent hydroxylation, bond cleavage and chlorination reactions led to the formation of more stable products. Three chlorinated intermediates were identified during ClO• oxidation process. Formation of the chlorinated disinfection by-products chloral hydrate and 1,1,1-trichloropropanone was enhanced relative to that of other by-products. The acute toxicity of gemfibrozil to Vibrio fischeri increased significantly when subjected to direct UV photolysis, whereas it decreased when oxidized by ClO•. This study is the first to report the transformation pathway of a micropollutant by ClO•.

Temperature-Induced Surface Effects on Drug Nanosuspensions.

PURPOSE: The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even though such interface effects can be of pharmaceutical relevance. Such potential effects in drug nanosuspensions were to be studied for temperatures of 25 and 37°C by using complementary surface analytical methods. METHODS: Atomic force microscopy, inverse gas chromatography and UV surface dissolution imaging were used together for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively. RESULTS: It was demonstrated that in case of bezafibrate nanosuspension, a surface modification occurred at 37°C compared to 25°C, which notably affected dissolution rate. By contrast, no similar effect was observed in case of fenofibrate nanoparticles. CONCLUSIONS: The combined usage of analytical surface methods provides the basis for a better understanding of phenomena that take place on drug surfaces. Such understanding is of importance for pharmaceutical development to achieve desirable quality attributes of nanosuspensions.

Direct observation of conformational population shifts in crystalline human hemoglobin.

Although X-ray crystallography is the most commonly used technique for studying the molecular structure of proteins, it is not generally able to monitor the dynamic changes or global domain motions that often underlie allostery. These motions often prevent crystal growth or reduce crystal order. We have recently discovered a crystal form of human hemoglobin that contains three protein molecules allowed to express a full range of quaternary structures, whereas maintaining strong X-ray diffraction. Here we use this crystal form to investigate the effects of two allosteric effectors, phosphate and bezafibrate, by tracking the structures and functions of the three hemoglobin molecules following the addition of each effector. The X-ray analysis shows that the addition of either phosphate or bezafibrate not only induces conformational changes in a direction from a relaxed-state to a tense-state, but also within relaxed-state populations. The microspectrophotometric O2 equilibrium measurements on the crystals demonstrate that the binding of each effector energetically stabilizes the lowest affinity conformer more strongly than the intermediate affinity one, thereby reducing the O2 affinity of tense-state populations, and that the addition of bezafibrate causes an ∼5-fold decrease in the O2 affinity of relaxed-state populations. These results show that the allosteric pathway of hemoglobin involves shifts of populations rather than a unidirectional conversion of one quaternary structure to another, and that minor conformers of hemoglobin may have a disproportionate effect on the overall O2 affinity.

Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques.

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways.

Evaluation of the simultaneous removal of recalcitrant drugs (bezafibrate, gemfibrozil, indomethacin and sulfamethoxazole) and biodegradable organic matter from synthetic wastewater by electro-oxidation coupled with a biological system.

Pharmaceutical degradation in conventional wastewater treatment plants (WWTP) represents a challenge since municipal wastewater and hospital effluents contain pharmaceuticals in low concentrations (recalcitrant and persistent in WWTP) and biodegradable organic matter (BOM) is the main pollutant. This work shows the feasibility of coupling electro-oxidation with a biological system for the simultaneous removal of recalcitrant drugs (bezafibrate, gemfibrozil, indomethacin and sulfamethoxazole (BGIS)) and BOM from wastewater. High removal efficiencies were attained without affecting the performance of activated sludge. BGIS degradation was performed by advanced electrochemical oxidation and the activated sludge process for BOM degradation in a continuous reactor. The selected electrochemical parameters from microelectrolysis tests (1.2 L s(-1) and 1.56 mA cm(-2)) were maintained to operate a filter press laboratory reactor FM01-LC using boron-doped diamond as the anode. The low current density was chosen in order to remove drugs without decreasing BOM and chlorine concentration control, so as to avoid bulking formation in the biological process. The wastewater previously treated by FM01-LC was fed directly (without chemical modification) to the activated sludge reactor to remove 100% of BGIS and 83% of BOM; conversely, the BGIS contained in wastewater without electrochemical pre-treatment were persistent in the biological process and promoted bulking formation.

Accumulation of pharmaceuticals in groundwater under arid climate conditions - Results from unsaturated column experiments.

Intense reuse of treated wastewater in agriculture is practiced all over the world, especially in arid and water-scarce regions. In doing so, pharmaceutical residues in the water are irrigated to the soil and subsequently can percolate into the local aquifers. Since evaporation rates in these areas are typically high, persistent substances might enrich in the groundwater recharge of closed catchments like the Jordan Valley. Against this background, unsaturated column tests were conducted to investigate the potential for evaporative accumulation of the two pharmaceuticals bezafibrate and carbamazepine under simulated arid climate conditions. Parallel tests were conducted with inhibited microbiological activity where both substances showed an increase in the effluent concentrations proportional to the evaporation loss of the inflow solution. The mean accumulation factors of the pharmaceuticals correspond to the evaporated water loss. The experiments indicate the accumulation potential for pharmaceuticals with high persistence against biodegradation. For the first time, the overall potential for evaporative enrichment could be demonstrated for pharmaceuticals. Under the given experimental conditions, the two investigated pharmaceuticals did not enrich faster than chloride, which might result in soil salting prior to reaching harmful pharmaceutical concentrations in soil water. The findings are relevant to future assessments of environmental impacts of persistent trace substances, which need to take into account that concentrations in the aquatic cycle might increase further due to evaporative enrichment.

Cerium doped red mud catalytic ozonation for bezafibrate degradation in wastewater: Efficiency, intermediates, and toxicity.

In this study, the performance of bezafibrate (BZF) degradation and detoxification in the aqueous phase using cerium-modified red mud (RM) catalysts prepared using different cerium sources and synthesis methods were evaluated. Experimental results showed that the surface cerium modification was responsible for the development of the catalytic activity of RM and this was influenced by the cerium source and the synthesis method. Catalyst prepared from cerium (IV) by precipitation was found to show the best catalytic activity in BZF degradation and detoxification. Reactive oxygen species including peroxides, hydroxyl radicals, and super oxide ions were identified in all reactions and we proposed the corresponding catalytic reaction mechanism for each catalyst that prepared from different cerium source and method. This was supported by the intermediates profiles that were generated upon BZF degradation. The surface and the structural properties of cerium-modified RM were characterized in detail by several analytical methods. Two interesting findings were made: (1) the surface texture (specific surface area and mesoporous volume) influenced the catalytic reaction pathway; and (2) Ce(III) species and oxygen vacancies were generated on the surface of the catalyst after cerium modification. This plays an important role in the development of the catalytic activity.

Ozonation of bezafibrate over ceria and ceria supported on carbon materials.

Two catalysts containing ceria dispersed on the surface of multi-walled carbon nanotubes and activated carbon were investigated as ozonation catalysts for the mineralization of bezafibrate (BZF). The results were compared with those obtained in the absence of the catalyst and in the presence of the parent carbon materials, as well as in the presence of ceria (CeO2). Carbon materials containing ceria showed an interesting catalytic effect. Both materials enhanced the mineralization of BZF relatively to single ozonation and ozonation catalysed by the corresponding carbon materials. In the catalytic ozonation with these materials, both surface and bulk reactions are supposed to occur. The BZF ozonation catalysed by CeO2 leaded to the highest mineralization degrees, indicating that the reaction mechanism followed in the presence of CeO2 (free radical oxidation in solution) leads to the formation of intermediates more easily degradable, mainly after 120 min of reaction. Some primary products and refractory final oxidation compounds in single and catalytic ozonation of BZF were followed. The original chlorine present on the BZF molecule is completely converted to chloride anion and part of the nitrogen is mainly converted to NO3- along with smaller amounts of NO2- and NH4+. Microtox tests revealed that simultaneous use of ozone and CeO2 originated lower acute toxicity.

Novel PPAR pan agonist, ZBH ameliorates hyperlipidemia and insulin resistance in high fat diet induced hyperlipidemic hamster.

Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1) activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC50, 1.75 µM) activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC50 37.37 µM) in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia.

Investigation of novel material for effective photodegradation of bezafibrate in aqueous samples.

A novel composite with an enhanced photocatalytic activity was prepared and applied to study the removal of bezafibrate (BZF), a hypolypemic pharmaceutical, from an aqueous environment. For the enhancement of titanium dioxide photoactivity a fullerene derivative, 2-(ferrocenyl) fulleropyrrolidine (FcC60), was synthesized and applied. Obtained composite was found to show a higher catalytic activity than pristine TiO2. Therefore, high hopes are set in composites that are based on carbonaceous nanomaterials and TiO2 as a new efficient photocatalysts.

Process design for wastewater treatment: catalytic ozonation of organic pollutants.

Emerging micropollutants have been recently the target of interest for their potential harmful effects in the environment and their resistance to conventional water treatments. Catalytic ozonation is an advanced oxidation process consisting of the formation of highly reactive radicals from the decomposition of ozone promoted by a catalyst. Nanocarbon materials have been shown to be effective catalysts for this process, either in powder form or grown on the surface of a monolithic structure. In this work, carbon nanofibers grown on the surface of a cordierite honeycomb monolith are tested as catalyst for the ozonation of five selected micropollutants: atrazine (ATZ), bezafibrate, erythromycin, metolachlor, and nonylphenol. The process is tested both in laboratorial and real conditions. Later on, ATZ was selected as a target pollutant to further investigate the role of the catalytic material. It is shown that the inclusion of a catalyst improves the mineralization degree compared to single ozonation.

[Preparation of red mud loaded Co catalysts: optimization using response surface methodology (RSM) and activity evaluation].

The removal efficiency of catalytic ozonation of bezafibrate (BZF) by red mud loaded Co catalysts (Co/RM) was used as the index value in statistical experimental designs. The most important factors influencing BZF degradation (P < 0.05) in water were dipping mass of cobalt and calcination temperature. Under the conditions of 4.14% of dipping mass of cobalt and 389 degrees C of calcination temperature, the BZF removal efficiency was 71.29% as calculated by predictive value and a maximum removal efficiency of 70.74% was actually achieved. The experiment data was very close to the predictive value and the deviation was 1% (< 5%). The results indicated that the response surface methodology and mathematical model was reliable for experimental design. By comparing the differences of BZF degradation in RM and Co/RM processes, it was observed that Co/RM exhibited the greater catalytic activity. Furthermore, the surface structure and composition properties of the two catalysts were evaluated by N2 adsorption, XRD and UV-Vis analysis. It was found that the specific surface area and total pore volume had the same variation trend, RM < Co/RM, which was consistent with the trend of catalytic ozonation. It was also found that Co3O4, the active component formed on the surface of RM by the addition of cobalt into red mud, enhanced the catalytic activity. Moreover, the dissolved metal concentration in the solution for catalytic ozonation of BZF degradation by RM or Co/RM was determined by ICP-OES. The results showed that for both catalysts there was no leaching of catalytic active components into the solution, which could suggest that the two catalysts were safe and could have certain application prospect.

Synthesis of highly water-soluble fibrate derivatives via BGLation.

Three water-soluble fibrates (fenofibrate, bezafibrate and chlofibrate) conjugated with a symmetrically branched glyceryl trimer (BGL003) were synthesized, and an evaluation of the fenofibrate-BGL003 conjugate as a candidate for anti-hyperlipemia drug was carried out using rats. The water-solubility of the fenofibrate-BGL003 conjugate was several thousand times greater than that of the original fenofibrate. The lipid-lowering effects of the fenofibrate-BGL003 conjugate were as strong as those of the same grams of fenofibrate. The actual active species of fenofibrate, fenofibric acid, was detected in rats' blood, but neither the fenofibrate-BGL003 conjugate nor fenofibrate was detected, probably due to enzymatic hydrolysis of the ester bond. The plasma concentration of fenofibric acid derived from the fenofibrate-BGL003 conjugate was five times higher than that derived from fenofibrate 4h after administration.

Binding of bezafibrate to human serum albumin: insight into the non-covalent interaction of an emerging contaminant with biomacromolecules.

In recent years, bezafibrate (BZF) has been frequently detected in environmental media. In order to reveal the toxicity of such an emerging pollutant, its interaction with human serum albumin (HSA) was studied by fluorescence spectrometry, circular dichroism, and equilibrium dialysis. Fluorescence data showed that the fluorescence quenching of HSA by BZF resulted from the formation of HSA-BZF complex. The binding constants were determined to be 3.33 × 10³, 2.84 × 10³ M⁻¹ at 298 and 309.5 K, respectively. The thermodynamic determination indicated that the hydrophobic and electrostatic interaction were the dominant binding force. The conformational investigation showed that the presence of BZF increased the α-helix content of HSA and induced the slight unfolding of the polypeptides of protein. Finally, the equilibrium dialysis showed that 0.56 mM BZF decreased the binding of vitamin B2 to HSA by 29%.

Comparison of APPI, APCI and ESI for the LC-MS/MS analysis of bezafibrate, cyclophosphamide, enalapril, methotrexate and orlistat in municipal wastewater.

The applicability of three different ionization techniques: atmospheric pressure photoionization (APPI), atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) was tested for the liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of five target pharmaceuticals (cyclophosphamide, methotrexate, bezafibrate, enalapril and orlistat) in wastewater samples. Performance was compared both by flow injection analysis (FIA) and on-column analysis in deionized water and wastewater samples. A column switching technique for the on-line extraction and analysis of water samples was used. For both FIA and on-column analysis, signal intensity and signal-to-noise (S/N) ratio of the target analytes in the three sources were studied. Limits of detection and matrix effects during the analysis of wastewater samples were also investigated. ESI generated significantly larger peak areas and higher S/N ratios than APCI and APPI in FIA and in on-column analysis. ESI was proved to be the most suitable ionization method as it enabled the detection of the five target compounds, whereas APCI and APPI ionized only four compounds.

Phenoxy herbicides and fibrates potently inhibit the human chemosensory receptor subunit T1R3.

We show that phenoxyauxin herbicides and lipid-lowering fibrates inhibit human but not rodent T1R3. T1R3 as a coreceptor in taste cells responds to sweet compounds and amino acids; in endocrine cells of gut and pancreas T1R3 contributes to glucose sensing. Thus, certain effects of fibrates in treating hyperlipidemia and type II diabetes may be via actions on T1R3. Likewise, phenoxy herbicides may have adverse metabolic effects in humans that would have gone undetected in studies on rodents.

Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extraction liquid chromatography coupled to polarity-switching electrospray tandem mass spectrometry.

We developed a rapid method for the monitoring of five selected pharmaceuticals in the influent and effluent of municipal wastewater treatment plants (WWTP) as well as in the effluent-receiving waters. To that end, we optimized and validated an analytical method based on on-line solid-phase extraction (on-line SPE) coupled with reversed-phase liquid chromatography-switching polarity electrospray ionization-tandem mass spectrometry (LC-ESI(+/-)-MS/MS). The target analytes have a variable hydrophobic character and belong to various therapeutic classes including the lipid regulator bezafibrate, the chemotherapy drugs methotrexate and cyclophosphamide, the lipase inhibitor orlistat and the angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension, enalapril. The method combines positive and negative voltage switching modes, therefore all analytes can be determined using a single injection and without any reduction in sensitivity. In order to detect traces of these compounds, a preconcentration step before detection is performed by loading 1.00 mL of sample in an on-line SPE cartridge and eluting from the cartridge using a reversed-phase liquid chromatography gradient. Analysis of wastewater and surface water samples was greatly affected by co-eluting matrix compounds, to compensate for matrix effects quantitation was therefore performed using standard additions. Method intra-day precision was less than 6.5% and limits of detection in fortified matrix effluent samples ranged from 9 to 20 ng L(-1). Four of the target pharmaceuticals were detected in the WWTP effluents, enalapril and bezafibrate being the most abundant compounds with concentrations of 35 and 239 ng L(-1), respectively. Concentrations of these same compounds in surface water samples from sites downstream in the St. Lawrence River were 8 and 63 ng L(-1), respectively, which was mainly due to dilution.

HPLC method for the determination of bezafibrate in human plasma and application to a pharmacokinetic study of bezafibrate dispersible tablet.

A sensitive and selective high-performance liquid chromatographic-UV (HPLC-UV) method for the determination of bezafibrate in human plasma has been developed. Sample treatment was based on protein precipitation with a perchloric acid-methanol solution 10:90 (v/v). Analytical determination was carried out by HPLC with UV detection at 235 nm. Chromatographic separation was achieved on a C18 column by isocratic elution with acetonitrile-ammonium acetate aqueous solution (10 mmol/L; pH 4.0) (44:56, v/v) at a flow rate of 1.0 mL/min. The method was linear in the concentration range of 0.1-15.0 microg/mL. The lower limit of quantitation was 0.1 microg/mL. The intra-and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 6.96%. The accuracy determined at three concentrations (0.2, 2.0, and 10.0 microg/mL for bezafibrate) was within +/- 10.0% in terms of accuracy. The method was successfully applied for the evaluation of pharmacokinetic profiles of bezafibrate dispersible tablet in 20 healthy volunteers. The results show that AUC, C(max), and T(1/2) between the testing formulation and reference formulation have no significant difference (P > 0.05). Relative bioavailability was 105.0 +/- 15.7%.