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PubMed1998

Metabolic effects and distribution space of flufenamic acid in the isolated perfused rat liver.

The following aspects were investigated in the present work: (a) the action of flufenamic acid on hepatic metabolism (oxygen uptake, glycolysis, gluconeogenesis, uricogenesis and glycogenolysis), (b) the action of flufenamic acid on the cellular adenine nucleotide levels, and (c) the transport and distribution space of flufenamic acid in the liver parenchyma. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, non-recirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. The distribution space of flufenamic acid was measured by means of the multiple-indicator dilution technique with constant infusion (step input) of [3H]water plus flufenamic acid. The results of the present work indicate that the metabolic effects of flufenamic acid are the consequence of an uncoupling of oxidative phosphorylation, a conclusion based on the following observations: (a) flufenamic acid increased oxygen uptake, a common property of all uncouplers; (b) the drug also increased glycolysis and glycogenolysis in livers from fed rats (these are expected compensatory phenomena for the decreased mitochondrial ATP formation); (c) flufenamic acid inhibited glucose production from fructose, an energy-dependent process; (d) the cellular ATP levels were decreased by flufenamic acid whereas the AMP levels were increased; and (e) the total adenine nucleotide content was decreased by flufenamic acid and uric acid production was stimulated. Indicator-dilution experiments with flufenamic acid revealed that this substance undergoes flow-limited distribution in the liver and that its apparent distribution space greatly exceeds the aqueous space of the liver. Flufenamic acid changed its behaviour when the portal concentration was increased from 25 to 50 microM. At 25 microM the initial upslope of the outflow profile clearly preceded that of all other concentrations. From the trend of the curves obtained with 50, 100 and 250 microM, one would expect an initial upslope situated at the right of the 50-microM curve. Furthermore, the time of appearance of flufenamic acid in the outflowing perfusate was practically the same irrespective of the portal concentration. For theoretical reasons one would expect progressively longer appearance times when the portal concentration was decreased. It is possible that the amount of flufenamic acid bound to the cell membranes during the early stages of the infusion produced changes that enabled these structures to bind a larger quantity of the drug than originally possible.

Adenine Nucleotides↗
PubMed1998

The effect of flufenamic acid on gastrointestinal myoelectrical activity and transit time in dogs.

BACKGROUND: Flufenamic acid, a fenamate, has been shown to alter markedly the membrane potential of small intestinal smooth muscle and increase intracellular calcium in single cells. AIMS: To determine the effects of flufenamic acid on myoelectrical motor activity and gastrointestinal transit in the intact animal. METHODS: Myoelectrical motor activity was recorded via seromuscular platinum electrodes sutured at regular intervals in the stomach and throughout the small intestine. Fasted and fed gastrointestinal transit was assessed using technetium-99m (99mTc) as the radioactive marker linked to 1 mm amberlite pellets or added to the meal. RESULTS: Flufenamic acid (600 mg, intravenously) induced intense spike activity in the small intestine. The mean duration of irregular spike activity was 250 (7) minutes. Spike activity was more pronounced in the lower small intestine. Flufenamic acid also accelerated initial gastric emptying and markedly shortened transit time in the small intestine. In the fasted state the 50% transit time in the small intestine was 54 (8) minutes with infusion of flufenamic acid compared with 105 (10) minutes in the control group; in the fed state 99mTc first reached the colon at 220 (10) minutes compared with 270 (12) minutes in the control group. CONCLUSIONS: Flufenamic acid had marked effects on both myoelectrical motor complex activity and small intestinal transit in the dog. The observed effects suggest that flufenamic acid may be of potential use as a prokinetic agent.

Animals↗
PubMed2006

Influence of nanoencapsulation on human skin transport of flufenamic acid.

The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrucken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.

Administration, Cutaneous↗
PubMed1999

The action of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the isolated perfused rat liver.

The influence of flufenamic acid and other nonsteroidal anti-inflammatories on sulfate transport in the liver was investigated. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, nonrecirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37 degrees C. Sulfate transport (equilibrium exchange) was measured by employing the multiple-indicator dilution technique with simultaneous injection (impulse input) of [35S]sulfate. [3H]sucrose (indicator for the distribution of the sinusoidal transit times), and [3H]water (indicator for the total aqueous space). Analysis was accomplished by means of a space-distributed variable transit time model. Flufenamic acid and other anti-inflammatories inhibited sulfate transport in the liver. For a concentration of 100 microM, the following decreasing series of potency could be established: flufenamic acid (53.4 +/- 2.9%) > niflumic acid (41.1 +/- 1.4%) > mefenamic acid (35.6 +/- 3.3%) > piroxicam (16.6 +/- 1.9%) > naproxen (13.5 +/- 8.4)%) nimesulide (11.6 +/- 5.8%). Inhibition of sulfate transport by flufenamic acid was clearly concentration dependent; 250 microM flufenamic acid produced more than 95% inhibition. Flufenamic acid in the range between 50 and 250 microM did not affect the mean transit times of tritiated water (t water) and [3H]sucrose (t suc), the same applying to all other anti-inflammatory agents (100 microM) tested in this work. This means that these agents do not affect vascular and cellular spaces, even when present at high concentrations. The ratio of the intra- to extracellular sulfate concentrations ([C]i/[C]e), generally between 0.4 and 0.5 under control conditions, was affected only by 250 microM flufenamic acid and 100 microM niflumic acid. In the first case, this phenomenon is possibly due to the high degree of transport inhibition (more than 95%), which does not allow a uniform tracer distribution over the whole cellular space during a single passage through the liver. The degree of inhibition of sulfate transport by 100 microM flufenamic acid was a function of the concentration of nontracer sulfate. With sulfate in the range between 1.2 and 25 mM, the inhibition degree increased linearly with the concentration. In the presence of flufenamic acid, the saturation curve of equilibrium exchange showed a substrate inhibition-like phenomenon, which was absent in the control curve. As inhibitors of sulfate transport in hepatocytes, flufenamic and niflumic acids are less active than in erythrocytes by a factor of 10(2). This observation is most probably indicative of structural differences between the hepatic sulfate carrier and the anion carrier of erythrocytes. It is unlikely that the action of flufenamic acid and its analogs on sulfate transport is a consequence of energy metabolism inhibition. Nimesulide is as active as flufenamic or niflumic acid in inhibiting energy metabolism but considerably less efficient as an inhibitor of sulfate transport. Our results as well as literature data reveal that the interactions of the nonsteroidal anti-inflammatories with the liver membranes and intracellular structures are ample and complex. Even at high concentrations, however, these interactions are not so intense as to change the vascular and cellular spaces.

Animals↗
PubMed2005

The effects of flufenamic acid on spontaneous activity of smooth muscle tissue isolated from the guinea-pig stomach antrum.

The effects of flufenamic acid were investigated on slow waves, follower potentials and pacemaker potentials recorded respectively from circular smooth muscle cells, longitudinal smooth muscle cells and interstitial cells of Cajal distributed in the myenteric layers (ICC-MY) of the guinea-pig stomach antrum. Flufenamic acid (>10(-5) M) inhibited the amplitude and rate of rise of the upstroke phase of the slow waves, with no marked alteration in their frequency of occurrence. The inhibitory actions of flufenamic acid appeared to be mainly on slow potentials recorded from circular smooth muscle cells, but not on follower or pacemaker potentials. After abolishing spontaneous slow potentials with flufenamic acid, depolarizing current stimuli could evoke slow potentials with an amplitude that was much smaller than in the absence of flufenamic acid, with no significant alteration to the input resistance of the membrane. The time elapsed for the generation of the 2nd component of the slow waves or the slow potentials evoked during depolarizing current pulse stimulation was increased by flufenamic acid. The rate of rise of unitary potentials, but not the frequency of occurrence, was inhibited by flufenamic acid. These results indicate that the inhibitory actions of flufenamic acid appear to be mainly on the circular muscle layer including the interstitial cells of Cajal distributed within the muscle bundles (ICC-IM). Nifedipine-sensitive spike potentials were not inhibited by flufenamic acid. It is concluded that the selective inhibition of the 2nd component of slow waves by flufenamic acid may be mainly due to the inhibition of ion channels, possibly Ca2+-sensitive Cl--channels, activated during generation of slow potentials in the ICC-IM distributed in the circular muscle layer.

Action Potentials↗
PubMed1992

Niflumic and flufenamic acids are potent inhibitors of chloride secretion in mammalian airway.

Effects of niflumic acid (NFA) and flufenamic acid (FFA), the two nonsteroid anti-inflammatory agents recently reported to inhibit Cl- current in Xenopus oocytes, were examined in cultured monolayers of dog and cow trachea. Both agents showed potent inhibition to the short-circuit current (Isc), an index of magnitude of transepithelial Cl- secretion, with values of Ki of 0.02 (for NFA) and 0.06 (for FFA) mM, respectively. The sensitivity sequence of Isc to the Cl- channel inhibitors tested was NFA > FFA > diphenylamine-2-carboxylate (DPC) >> anthracene-9-carboxylate (A9C). Thus, NFA and FFA are so far the most potent commercially available Cl- channel inhibitors tested in Cl(-)-secreting epithelia. The sensitivity sequence of 36Cl uptake to the above Cl- channel inhibitors in Xenopus laevis oocytes was found to be identical to the cultures of trachea. This seems to imply that the membrane Cl- channels of Xenopus oocytes are functionally similar to that identified in mammalian Cl(-)-secreting epithelia.

Animals↗
PubMed2001

Flufenamic acid enhances current through maxi-K channels in the trabecular meshwork of the eye.

PURPOSE: Flufenamic acid relaxes trabecular meshwork, a smooth muscle-like tissue involved in the regulation of ocular outflow in the eye. In this study, we attempted to determine if ionic channels are involved in this response. METHODS: Cultured human (HTM) and bovine (BTM) trabecular meshwork cells were investigated using the patch-clamp technique. RESULTS: In trabecular meshwork, flufenamic acid (10(-5) M) reversibly stimulated outward current to 406 +/- 71% of initial outward current level in BTM (n = 10) and 294 +/- 75% of initial current level in HTM (n = 12) in all cells investigated; no significant differences emerged. The response was dosage-dependent. Replacement of potassium in all solutions eliminated the response to flufenamic acid (n = 4, BTM). Blocking K(ATP ) channels with glibenclamide (10(-5) M, n = 6) and small-conductance calcium-activated potassium channels with apamin (10(-6) M, n = 5) had no effect. A direct effect on calcium channels could also not be detected. Blockage of the large-conductance calcium-activated potassium channel (maxi-K) by iberiotoxin (10(-7) M) suppressed 87 +/- 9% (n = 6; HTM) and 91 +/- 10% (n = 6; BTM) of the response. Depleting the cells of calcium did not significantly alter the response to flufenamic acid. CONCLUSIONS: Flufenamic acid stimulates maxi-K channels in trabecular meshwork of both human and bovine origin. This should lead to hyperpolarization, closure of L-type channels and lowered cytosolic calcium levels, possibly explaining the relaxation observed in response to this substance.

Animals↗
PubMed1992

Interaction of the non-steroidal anti-inflammatory drug flufenamic acid with gastric acid secretion and H+/K(+)-ATPase.

1. The effects of the non-steroidal anti-inflammatory drug (NSAID) flufenamic acid on H+ production in isolated and enriched guinea-pig parietal cells and on H+/K(+)-ATPase activity in ion-tight inside-out membrane vesicles from pig gastric mucosa were studied. 2. At low concentrations (0.1 and 1.0 mumol/L), flufenamic acid increased the secretory response of parietal cells to dibutyryl cyclic AMP (dbcAMP). At higher concentrations (10 and 100 mumol/L) it progressively inhibited basal and dbcAMP-stimulated acid production. 3. Flufenamic acid (10 mumol/L) increased K+ (0.5-10.0 mmol/L) and K+ (0.5-1.0 mmol/L) plus gramicidin-stimulated ATPase activity in gastric membrane vesicles. The Km value for K+ (1.6 and 1.0 mmol/L in the absence and presence of gramicidin, respectively) was decreased to 0.8 and 0.5 mmol/L, respectively. At higher concentrations (greater than or equal to 50 mumol/L), flufenamic acid inhibited K+ plus gramicidin-stimulated ATPase activity (inhibited concentration at 50% [IC50] = 186 mumol/L) and reduced the proton concentration (IC50 = 50 mumol/L). 4. It is concluded that flufenamic acid-induced enhancement of dibutyryl cyclic AMP-stimulated H+ production in the parietal cell reflects the stimulation of H+/K(+)-ATPase. We suggest that activation of the enzyme involves increased affinity of K+ towards the K(+)-binding site of the enzyme and/or increased KCl permeability at the vesicle membrane. The inhibitory action of the drug on H+ production in parietal cells results from a detergent and/or protonophoric-like action at the apical parietal cell membrane, and from inhibition of H+/K(+)-ATPase activity.

Adenosine Triphosphatases↗
PubMed1975

Inhibition of prostaglandin synthetase and carrageenan-induced edema by tricyclic analogs of flufenamic acid.

A group of tricyclic analogs of flufenamic acid were tested for their ability to inhibit both the biosynthesis of prostaglandin and carrageenan-induced inflammation of the rat paw. All had activity greater than phenylbutazone as inhibitors of prostaglandin synthetase, with SK&F 22908 being as active as flufenamic acid. The anti-inflammatory activities of these compounds correlated only to a minor degree with the inhibition of prostaglandin biosynthesis. The data support the position that within this series of compounds inhibition of prostaglandin synthetase and non-steroidal antiinflammatory activity, as well as ulcerogenic liability, may be an expression of different mechanisms.

Animals↗
PubMed2000

Flufenamic acid as an inducer of mitochondrial permeability transition.

To assess the mechanism by which mitochondrial permeability transition (MPT) is induced by the nonpolar carboxylic acids, we investigated the effects of flufenamic acid (3'-trifluoromethyl diphenylamine-2-carboxylic acid, FA) on mitochondrial respiration, electrical transmembrane potential difference (delta psi), osmotic swelling, Ca2+ efflux, NAD(P)H oxidation and reactive oxygen species (ROS) generation. Succinate-energized isolated rat liver mitochondria incubated in the absence or presence of 10 microM Ca2+, 5 microM ruthenium red (RR) or 1 microM cyclosporin A (CsA) were used. The dose response-curves for both respiration release and delta psi dissipation were nearly linear, presenting an IC50 of approximately 10 microM and reaching saturation within 25-50 microM, indicating that FA causes mitochondrial uncoupling by a protonophoric mechanism. Within this same concentration range FA showed the ability to induce MPT in energized mitochondria incubated with 10 microM Ca2+, followed by delta psi dissipation and Ca2+ efflux, and even in deenergized mitochondria incubated with 0.5 mM Ca2+. ADP, Mg2+, trifluoperazine (TFP) and N-ethylmaleimide (NEM) reduced the extent of FA-promoted swelling in energized mitochondria by approximately one half, whereas dithiothreitol (DTT) slightly enhanced it. NAD(P)H oxidation and ROS generation (H2O2 production) by mitochondria were markedly stimulated by FA; these responses were partly prevented by CsA, suggesting that they may be implicated as both a cause and effect of FA-induced MPT. FA incubated with mitochondria under swelling assay conditions caused a decrease of approximately 40% in the content of protein thiol groups reacting with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). The present results are consistent with a ROS-intermediated sensitization of MPT by a direct or indirect FA interaction with inner mitochondrial membrane at a site which is in equilibrium with the NAD(P)H pool, namely thiol groups of integral membrane proteins.

Animals↗
PubMed2002

Flufenamic acid: growth modulating effects on human aortic smooth muscle cells in vitro.

PURPOSE: The aim of the study was to examine the effects of flufenamic acid on proliferation, clonogenic activity, migratory ability, cell-cycle distribution, and p44/42-mitogen-activated protein kinase (MAPK) expression on serum-stimulated human aortic smooth muscle cells (haSMCs) in vitro. MATERIALS AND METHODS: HaSMCs were treated with flufenamic acid in three different doses (40 micromol/L, 200 micromol/L, 400 micromol/L) for 4 days, and then flufenamic-acid-free culture medium was supplemented every 4 days until day 20 after initial treatment. The growth kinetics were assessed. Cell-cycle analysis was performed by flow cytometry. The clonogenic activity was evaluated with use of colony formation assays. The migratory ability was investigated by stimulation with platelet derived growth factor (PDGF-BB) in 24 well plates with 8-microm pore membrane inserts. The p44/42 MAPK was detected by Western blot technique. RESULTS: Flufenamic acid inhibited the proliferation (400 micromol/L treatment over 4 d; 179,700 +/- 49,800 vs 747,900 +/- 144,000; P <.001), clonogenic activity (400 micromol/L treatment over 4 d; 1 +/- 0.3 vs 50 +/- 1.4; P <.001) and migratory ability (400 micromol/L treatment over 4 d; 8 cells +/- 2 vs 48 cells +/- 15; P <.001) of haSMCs in a dose-dependent manner. Cell-cycle analysis revealed a G2/M-phase block (400 micromol/L treatment over 4 d; 28.9 +/- 1.5 vs 9.5 +/- 3.2; P <.001). The expression of p44/42 MAPK was reduced for a treatment with 400 micromol/L flufenamic acid (controls, 427 BLU +/- 0.305 vs treatment group, 190 BLU +/- 106; P <.05) CONCLUSION: Flufenamic acid inhibits the proliferation and migration of haSMCs. Further experiments with animal models concerning stenosis and restenosis are necessary to evaluate the potential of this promising drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1983

Percutaneous absorption of flufenamic acid in rabbits: effect of dimethyl sulfoxide and various nonionic surface-active agents.

Eight nonionic surface-active agents were each incorporated at a concentration of 10% into a white petrolatum ointment base containing 10% flufenamic acid with or without dimethyl sulfoxide. Percutaneous absorption was studied by determining the plasma concentration of flufenamic acid in New Zealand White rabbits at regular intervals for 8 hr following application of the ointment. The percutaneous absorption of flufenamic acid was significantly increased when sorbitan trioleate, polyoxyl 8 stearate, or polyoxyethylene 2 oleyl ether were added to the ointment containing flufenamic acid and white petrolatum. The percutaneous absorption of flufenamic acid was increased significantly when sorbitan monopalmitate, sorbitan trioleate, polyoxyl 8 stearate, polyoxyethylene 20 cetyl ether, or polyoxyethylene 2 oleyl ether were added to the ointment containing dimethylsulfoxide, flufenamic acid, and white petrolatum.

Animals↗
PubMed2002

Effects of flufenamic acid on smooth muscle of the carotid artery isolated from spontaneously hypertensive rats.

Endothelium-removed carotid artery strips from stroke-prone spontaneously hypertensive rats spontaneously developed a tonic myogenic contraction. Flufenamic acid reduced the resting tone observed during superfusion with Tyrode's solution, in a concentration-dependent manner. Flufenamic acid also inhibited contractions produced by high-K solutions in a concentration-dependent manner. The resting membrane potential of smooth muscle cells in the artery was around -32 mV, with occasional oscillatory potentials. Flufenamic acid hyperpolarized the membrane in a concentration-dependent manner. The voltage-dependent outward currents recorded in isolated cells with micropipettes filled with high-K+ solution (holding potential, -60 mV) were enhanced by flufenamic acid and inhibited by tetraethylammonium. When the recording micropipette was filled with high Cs to inhibit the K+-current, depolarizing step pulses evoked nifedipine-sensitive inward currents. Flufenamic acid inhibited the inward currents. These results indicate that flufenamic acid inhibits the spontaneous active tone of the carotid artery by inhibiting L-type Ca2+-channels and possibly by membrane hyperpolarization through activation of the voltage-dependent K+-channels.

Animals↗
PubMed1985

Reversible hyperkalemia induced by flufenamic acid in asymptomatic hyporeninemic patient.

Reversible hyperkalemia induced by flufenamic acid in an asymptomatic hyporeninemic patient with IgA nephropathy is reported. Flufenamic acid, 600 mg daily, was given for four months to a 64-year-old woman with biopsy proven IgA-nephropathy. This produced hyperkalemia, hypertension and congestive heart failure with slowly progressive renal impairment. We conclude that a further suppression of the renin angiotensin system causing selective hypoaldosteronism together with the nephrotoxic effects of this drug may have been responsible for hyperkalemia in this patient.

Female↗
PubMed1983

Studies on flufenamic acid capsules and tablets.

In this study, the in vitro dissolution rate of flufenamic acid was investigated in two different dosage forms, tablets and capsules, and the influence of the commonly used additives (lactose, corn starch, magnesium stearate, sodium lauryl sulphate). Using lactose, starch, Avicel PH 101, and methyl cellulose as additives, direct compression and wet granulation techniques were tried for preparing flufenamic acid tablets. The rotating basket method of U.S.P. XIX was used for determination of release rate. The findings were compared to the dissolution rate results of the commercial flufenamic acid capsules.

Capsules↗
PubMed1984

pH-induced difference spectrophotometric methods for drug analysis. Part 2: Determination of mefenamic and flufenamic acid.

On the basis of the spectral changes induced by changing the solvent medium from HCl (0.01 mol . l-1) to NaOH (0.01 mol . l-1), coefficient-difference spectrophotometric methods using the six-points quadratic order of the orthogonal polynomials have been developed. The optimum wavelength ranges were 326 to 386 nm for mefenamic acid and 322 to 382 nm for flufenamic acid, both measured at 12 nm intervals. The respective mean percentage recoveries were 100.1 +/- 0.89 over a concentration range of 0.6-2.6 mg/100 ml of mefenamic acid and 100.7 +/- 0.61 over a range of 0.2-2.4 mg/100 ml for flufenamic acid (p = 0.05). Both methods gave precise results with relative standard deviation less than 1%. Trials to adapt single wavelength difference technique as well as the cubic order of the orthogonal polynomials were also performed; their results were discussed on a statistical basis. The developed procedures have been applied to the analysis of some randomly collected market preparations and the results obtained proved suitability for application in routine analysis.

Capsules↗
PubMed2006

Inhibition of eryptosis and intraerythrocytic growth of Plasmodium falciparum by flufenamic acid.

Non-selective (NSC) cation channels participate in the Ca(2+) leak of human erythrocytes. Sustained activity of these channels triggers suicidal erythrocyte death (eryptosis), which is characterized by Ca(2+)-stimulated cell shrinkage and phosphatidylserine (PS) exposure. PS-exposing erythrocytes are rapidly cleared from circulating blood. PGE(2) activates the NSC channels, and erythrocyte PGE(2) formation is stimulated by a decrease in intra- or extracellular Cl(-) concentration. In addition, the intraerythrocytic malaria parasite Plasmodium falciparum activates the NSC channels, most probably to accomplish Na(+) and Ca(2+) entry into the erythrocyte cytosol required for parasite development. By Ca(2+) uptake the parasite maintains a low Ca(2+) concentration in the erythrocyte cytosol and thus delays the suicidal death of the host erythrocyte. Flufenamic acid has previously been shown to inhibit NSC channels. The present study thus explored the effect of flufenamic acid on erythrocyte Ca(2+) entry, on suicidal erythrocyte death and on intraerythrocytic growth of P. falciparum. Within 48 h, replacement of extracellular Cl(-) with gluconate or application of PGE(2) (50 microM) increased Fluo3 fluorescence reflecting cytosolic Ca(2+) activity, decreased forward scatter reflecting cell volume and increased annexin V binding reflecting PS exposure in FACS analysis. All those effects were significantly blunted in the presence of flufenamic acid (10 microM). Flufenamic acid (25 microM) further significantly delayed the intraerythrocytic growth of P. falciparum and the PS exposure of the infected erythrocytes. The present observations disclose a novel effect of flufenamic acid, which may allow the pharmacological manipulation of erythrocyte survival and the course of malaria.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Effect of particle size and film thickness on bioavailability and ulcerogenicity of encapsulated flufenamic acid.

Encapsulation of four batches of flufenamic acid (FFA) having mean particle diameters of 75, 130, 180 and 225 microns with cationic acrylic resin (Eudragit E) have been achieved using a fluidized-bed granulator (Glatt AG). The bioavailability and gastric ulcerogenic activity of the encapsulated and plain drug for each batch have been simultaneously assessed in rats subjected to physical restraint stress. Encapsulated batches of FFA showed significantly higher plasma levels and lower ulcerogenic activities than those of plain batches. Although encapsulated batches showed comparable plasma levels, compared with each other, they varied greatly as regards their ulcerogenic activities. The smaller the mean diameter of microcapsules of a batch the lower its ulcerogenic activity. A linear correlation was found between the film thickness of Eudragit in microcapsules and the ulcer indices of various encapsulated batches. Plain FFA batches, however, showed comparable plasma levels as well as comparable ulcer data, when compared with each other, within the size range studied.

Animals↗