Interaction Of Naproxen Research Articles

Efficient fluorescence probe for detection of naproxen in pharmaceutical formulations and water samples using MPA-capped CdTe/ZnS core-shell nanocrystal-neutral red: Experimental and computational studies

The distinct optical properties of surface-engineered quantum dots, featuring high fluorescent quantum yields and biocompatibility, render them valuable tools for precise and selective sensing and biosensing applications spanning diverse fields, including medicine, environmental monitoring, and diagnostics. In this study, we have successfully fabricated a new “OFF-ON” fluorescent probe based on 3-mercaptopropionic acid (MPA) - capped CdTe/ZnS QDs and neutral red (NR) for the determination of Naproxen (NAP) in pharmaceutical formulations and water samples. The as-prepared MPA-TGA-CdTe/ZnS QDs exhibit a robust photoluminescent emission, peaking at 544 nm upon excitation with a 380 nm wavelength. The quantum yield measurement for the TGA-CdTe QDs was ascertained to be 29.3 %. The findings displayed that the fluorescence emission of MPA-TGA-CdTe/ZnS quantum dots (QDs) could be significantly quenched by increasing neutral red concentration, which can be attributed to the formation of non-fluorescent NR- MPA-TGA-CdTe/ZnS QDs complex (NR-MPA energy level 1.15 Kcal/mol). Upon the addition of naproxen, there was a noticeable enhancement in fluorescence intensity because of the formation of the strong complex between naproxen and NR (NR-NAP energy level: −1.54 Kcal/mol), leading to the detachment of NR from the surface of quantum dots. Consequently, the MPA-TGA-CdTe/ZnS QDs became activated, resulting in the restoration of fluorescence intensity of MPA-TGA-CdTe/ZnS QDs. The enhancement of fluorescence intensity exhibited a direct relationship with the concentration of naproxen, following a linear trend within the concentration range of 2.00 × 10−1 to 27.3 µmol/L with the detection limits of 7.0 × 10−2 µmol/L. Moreover, computational studies were also used to validate the MPA-TGA-CdTe/ZnS QDs turn-off-ON sensor for sensing naproxen. The interactions of NAP, NR, and MPA-TGA-CdTe/ZnS QDs made a solid base for controlling the fluorescent reversibility of QDs. The as-prepared quantum dots were subjected to cytotoxicity studies using an MTT assay and AAS technique. These findings revealed that MPA-TGA-CdTe/ZnS QDs have greater biocompatibility and lower toxicity, making them attractive for biological applications. The recoveries of naproxen detection using the proposed fluorescent probe in various pharmaceutical formulations and water samples ranged from 97.4 % to 102 %, with a relative standard deviation of less than 5 %.

Unraveling the Role of Drug-Lipid Interactions in NSAIDs-Induced Cardiotoxicity.

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers’ structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity.

Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats

Ethnopharmacological relevanceAndrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug. Aim of the studyTo evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats. Materials and methodsAfter oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. ResultsCo-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The Cmax, tmax, AUC0−t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone. ConclusionThe results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb–drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb–drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb–drug interaction in humans.

Interaction of naproxen with calcium carbonate: physicochemical characterization and in vitro drug release studies

Interaction and physicochemical characterization of dispersions of naproxen in calcium carbonate after freeze-drying the wet-state equilibrated mixture have been investigated by analytical methods. The FT-IR study revealed the acid-base reaction between naproxen and calcium carbonate. The DSC study indicated physical interaction and significantly diminished crystallinity of naproxen in the formulation containing higher quantities of calcium carbonate. Furthermore, the SEM study showed the reduced particle size and loss of crystalline morphology in the same sample. Drug release increased with the increase of calcium carbonate in the formulations. Formulation of naproxen with calcium carbonate in 1:2 ratio allowed its dissolution to the greatest extent (94.96%) while other compositions, 1:0.5 and 1:1, showed 80.86% and 78.30% release, respectively.

Can compression induce demixing in amorphous solid dispersions? A case study of naproxen–PVP K25

The aim of this work is to investigate the effect of compression on miscibility of naproxen (NAP)–PVP K25 solid dispersions. Solid dispersions with diverse drug/polymer compositions were compressed at various forces for uniform dwell time. Miscibility assessments were performed using mDSC, and the effect of compression on the specific interactions of NAP and PVP K25 was investigated by FTIR. The 20% (w/w) naproxen containing solid dispersion showed a single Tg before and after compression. FTIR analysis showed the unchanged profile of this system upon compression. On the other hand, the miscibility in the compositions with 30% and 40% (w/w) naproxen is markedly affected by compression. Compression pressures from beyond 565.05MPa induced apparent amorphous–amorphous phase separation as indicated by two characteristic Tgs in DSC and altered IR spectral profile. The highly ductile nature of PVP promotes plastic deformation upon compression induced by the rotation of the PVP backbone with the transition of dihedral angles from low to high energy state. Segmental rotation can also be an outcome of plastic deformation that often leads to increase in structural temperature. This can have influence on miscibility resulting from weakening and/or disruption of intermolecular hydrogen bonding between drug and polymer upon compression.

β-Cyclodextrin hydrogels as potential drug delivery systems

► Insoluble cyclodextrin polymers as discs with a controlled geometry have been synthesized. ► Interaction between the polymers and model drugs in the solid state canbe evidenced. ► Kinetic, diffusion constants and diffusion coefficients have been calculated. ► In vitro drug release studies followed a simple Fickian diffusion mechanism. ► The synthesized matrices are potentially suitable as sustained release systems. β-cyclodextrins (βCD) are cyclic oligosaccharides which have been widely employed for pharmaceutical applications. Discs of insoluble polymers were synthesized by crosslinking β-cyclodextrins with the reagent epichlorohydrin. In this work, the possibility of employing a polymer containing 60 ± 3% βCD for drug delivery of two antiinflammatory (naproxen and nabumetone) and two antifungal drugs (naftifine and terbinafine) has been investigated. The interaction of Naproxen with the polymers was evidenced by X-ray diffractometry, FTIR spectroscopy and differential thermal analysis. Drug release kinetics were carried out at physiological conditions of pH and temperature, and kinetic and diffusion constants were calculated by fitting 60% of the release profile according to the Korsmeyer–Peppas equation. Also, diffusion coefficients were calculated according to the simplified Higuchi model. The drug release followed a simple Fickian diffusion mechanism for all the model drugs. This study suggests that these hydrogel matrices are potentially suitable as sustained release systems.

Interaction of naproxen with β-cyclodextrin and its derivatives/polymer: experimental and molecular modeling studies

The interaction of naproxen with β-cyclodextrin and its derivatives (hosts) as well as polymer has been studied using UV Visible (UV–Vis), Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning electron microscopy (SEM). In this paper, the solid inclusion complexes were prepared by freeze drying method. The formation constants of the complexes were determined by UV–Vis method. The adsorption properties of naproxen with β-Cyclodextrin bonded silica stationary phase (CDS) were studied for an in-depth understanding of the host–guest interaction. The inclusion process involving naproxen and hosts was investigated by using the PM3 quantum–mechanical semiempirical method. The stabilization energy values obtained from the semiempirical calculation showed the same relation with the formation constant values determined by UV–Vis spectroscopy.

Interaction of Naproxen with transition metals: synthesis, characterization, anti-inflammatory activity and kinetic studies

Coordination complexes of transition metals (Co, Ni, Cu, Fe, Cr, Ru, Ir, Mn, and Zn) with 6-methoxy-α-methyl-2-naphthalene acetic acid (Naproxen) and triphenylphosphine have been synthesized and characterized by conductance, elemental analysis, UV-Vis, AAS, and FT-IR spectroscopy. The elemental analyses data reveal the presence of 1:1 (metal : ligand) stoichiometry and the IR data suggest that naproxen functions as a bidentate ligand in coordination with transition metals. The anti-inflammatory assays of these complexes have significant effect.

Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state

The possible role of the cyclodextrin charge in the interaction with an acidic drug such as naproxen (p K a 4.8) has been evaluated. Sulfobutylether-ß-cyclodextrin (SBE-ßCyd) and trimethylammonium-ß-cyclodextrin (TMA-ßCyd) were selected as, respectively, anionically and cationically charged carriers and their performance was compared with that of the parent ß-cyclodextrin (ßCyd) and of its methyl-derivative (MeßCyd) previously found as the best partner for the drug. Interactions in solution were investigated by phase-solubility, fluorescence and circular dichroism analyses. Equimolar drug–carrier products prepared by different techniques (blending, cogrinding, sealed-heating, colyophilization) were characterized by differential scanning calorimetry and X-ray powder diffractometry and tested for drug dissolution properties. Anionic charges of SBE-ßCyd did not negatively influence interactions in unbuffered aqueous solutions (pH ≈5) with the acidic drug. In fact, it was a very effective carrier, exhibiting solubilizing and complexing properties considerably better than the parent ßCyd and comparable to those of MeßCyd. On the contrary, the positive charges of TMA-ßCyd did not favour interactions with the counter-ionic drug (despite the presence of about 60% ionised drug) and it was less efficacious also than native ßCyd. Therefore, the role of the Cyd charge on the complexing and solubilizing properties towards naproxen was not important whereas other factors, such as steric hindrance effects and favourable hydrophobic interactions were significant in determining the drug affinity for the Cyd inclusion. Solid state studies evidenced similar amorphizing properties of both charged Cyds towards naproxen. On the other hand, dissolution tests, in agreement with solution studies, showed that all products with SBE-ßCyd exhibited significantly better dissolution properties than the corresponding ones with TMA-ßCyd. A clear influence of the preparation method of drug–Cyd solid systems on the performance of the end product was also observed. Colyophilization was the most effective technique, followed by the cogrinding one. Colyophilized product with SBE-ßCyd allowed a 10-times increase in drug dissolution efficiency (D.E.) (with respect to the five-times increase obtained with the corresponding coground product) and a reduction of t 50% from about 60 min (for the coground product) to less than 2 min.

Interaction of naproxen with noncrystalline acetyl β- and acetyl γ-cyclodextrins in the solid and liquid state

Randomly acetylated, amorphous β-cyclodextrin (AcβCd) and γ-cyclodextrin (AcγCd), having an average substitution degree per anhydroglucose unit, respectively, of 1.1 and 0.95 (∼7.7 acetyl residues per macrocycle), were investigated for their interactions in the solid and liquid state with naproxen (NAP). Differential scanning calorimetry (DSC), supported by X-ray powder diffractometry (XRD), of NAP–AcβCd and NAP–AcγCd blends revealed an apparent decrease in drug crystallinity which was related to a heating-induced solid-state interaction between the drug and each carrier. A solubility of ∼0.40 NAP mass fraction in amorphous AcβCd and amorphous AcγCd at room temperature was determined. Phase-solubility analysis at 25, 37, and 45°C accounted for A L-type inclusion complexation of NAP with AcβCd ( K 1:1,25°C=4.5(4)×10 3 l mol −1) and AcγCd ( K 1:1,25°C=0.80(7)×10 3 l mol −1) and revealed a solubilizing efficiency of AcβCd toward NAP ∼4 times that of AcγCd. Equimolar drug–carrier combinations prepared from the respective blends by grinding, kneading, coevaporation and freeze-drying were characterized by DSC and XRD and tested for dissolution rate of NAP using the dispersed amount and continuous flow through methods. The best performance in terms of dissolution rate enhancement (∼23 times and ∼10 times the dissolution efficiency of pure drug in the dispersed amount and continuous flow through tests, respectively) was displayed by the NAP–AcβCd colyophilized product.

Interaction of Naproxen with Crystalline and Amorphous Methylated β-Cyclodextrin in the Liquid and Solid State

Interactions of naproxen (NAP) with amorphous, randomly methylated β-cyclodextrin at a degree of substitution per anhydroglucose unit of 1.8 (RAMEB) and with crystalline heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) were studied in aqueous solution and in the solid state using, respectively, phase-solubility analysis (at 25 °C, 37 °C and 47 °C) and differential scanning calorimetry (DSC) supported by X-ray powder diffractometry. RAMEB and DIMEB displayed similar solubilizing and complexing abilities towards NAP, suggesting analogous inclusion modes of the drug in the host cavity in aqueous solution. Differences were instead observed in interactions in the solid state, where the amorphizing capacity of RAMEB toward NAP (evaluated by DSC) was about twice that of DIMEB at each drug-to-carrier ratio. Assuming that inclusion complexation is also involved in solid-state interactions, molecular modelling accounted for the experimental results in terms of structural features of DIMEB, i.e. the particular inwards orientation of O-6-C-8 groups of three alternate glucoses on the primary hydroxyl side which hampers a deep penetration of NAP in the DIMEB cavity in the solid state. On the contrary, no obstruction of the cavity apparently occurs with RAMEB due its noncrystalline state. The aqueous dissolution rate of NAP from NAP-RAMEB and NAP-DIMEB blends containing 0.59, 0.73, 0.85, and 0.92 mass fraction of carrier linearly increased at decreasing drug-to-carrier ratios. The improvement was 5 to 20 times (from powders) and 50 to 200 times (from discs) the dissolution rate of NAP alone for both carrier. Therefore the choice of the amorphous RAMEB in pharmaceutical formulations can be recommended mainly for economic reasons, though the anhydrous and non-hygroscopic nature of crystalline DIMEB might be of particular advantage in case of moisture sensitive formulations.

Interaction of naproxen with alpha-cyclodextrin and its noncyclic analog maltohexaose.

To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with alpha-cyclodextrin (alphaCd), amorphous alphaCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution. NAP-additive physical mixtures at 0.30, 0.18, and 0.10 mass fraction of drug were tested, after increasing grinding times, by differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Interaction in aqueous solution was examined by phase-solubility and fluorescence analyses supported by molecular modelling. In the mixtures with each additive the fusion enthalpy per unit mass of NAP decreased and the half width at half maximum of selected X-ray diffraction peaks of NAP increased with the progress of grinding time following the loss of crystallinity of the samples. The mechanical treatment apparently did not affect the chemical integrity of the drug. Particularly active in the equimolar mixture was the best amorphizing agent, M6. Solution studies and molecular modelling confirmed M6 may have the feature of a supermolecule for NAP, which forms a 1:1 pseudo-inclusion complex that was as stable as the true inclusion complex with alphaCd. The intrinsically amorphous linear analog of aCd might be a potential amorphism-inducing agent and solubilizer for scarcely water soluble drugs.

A fluorimetric, potentiometric and conductimetric study of the aqueous solutions of naproxen and its association with hydroxypropyl- β-cyclodextrin

The dissociation constant, K a, of naproxen, a nonsteroidal antiinflammatory drug of the family of arylpropionic acids, has been determined in aqueous solutions at 25°C by using a potentiometric and a conductimetric techniques. The solubility limit of the drug in water, a controversial point in the literature, has been found to be less than 3×10 −5 M. The interaction of naproxen with hydroxypropyl- β-cyclodextrin (HPBCD), in terms of the binding constants of the complexes formed by the CD and the nonionic (HNAP) and ionic (NAP −) species of the drug, has been evaluated at 25°C as well by means of steady-state fluorescence enhancement studies. A discussion of the results, K HPBCD:HNAP=6500±400 M −1 and K HPBCD:NAP−=1400±80 M −1, emphasizing the crucial importance of the choice of the pH at a value that pH≥p K a +2 or pH≤p K a −2, is also included.

Interactions between naproxen and maltoheptaose, the non-cyclic analog of?-cyclodextrin

The crystallinity of naproxen in solid combinations with amorphous maltoheptaose, the non-cyclic analog of β-cyclodextrin, was assessed using differential scanning calorimetry supported by X-ray powder diffractometry. Cogrinding induced a decrease in drug crystalinity to an extent which depended on the grinding time, and was most pronounced for the combination of equimolecular composition. Thermal analysis showed that the mechanism behind the conversion of crystalline naproxen into the amorphous state by cogrinding with maltoheptaose differed from that with randomly substituted, amorphous β-cyclodextrins. Interactions of naproxen with maltoheptaose in aqueous solution were studied by means of fluorescence spectroscopy, phase-solubility analysis, and computeraided molecular modelling. Maltoheptaose can wrap up naproxen, taking on a cyclic conformation and forming a ‘pseudo’ inclusion complex (apparent binding constant K1: 1 = 1.0 × 103 (−20%) L mol−1 at 25 °C) which is about as stable as the true inclusion complex with β-cyclodextrin in the lowest temperature range (0-100 K). A better complexing ability for naproxen in terms of binding constant values, however, was displayed by both native and derivatized β-cyclodextrins, the ‘hosts’ with covalently-bound cyclic structures.

Fast Determination of Naproxen in Serum by Stopped-Flow/Room Temperature Liquid Phosphorimetry

Abstract The stopped-flow mixing technique was used to develop an automated room-temperature liquid phosphorimetric method for the straightforward, fast determination of naproxen in serum samples. The interaction of naproxen with thallium(I) ions in the presence of sodium dodecyl sulfate allows one to obtain a kinetic curve that levels off within only 2 s. This approach allows the development of very fast kinetic and equilibrium methods by using the slope and amplitude of the kinetic curve, which are directly proportional to the naproxen concentration, as analytical parameters. The linear calibration range thus achieved is 0.06-15 or 0.08-15 μg mL−1, depending on wheather slope or amplitude measurements are used. The within- and between-assay precision data, as well as the selectivity of the method are more than adequate for the determination of naproxen in serum samples pretreated with acetonitrile. Analytical recoveries range from 90.7 to 104.0%.

Interaction of naproxen with ?-, ?-, and ?-hydroxypropyl cyclodextrins in solution and in the solid state

Solid combinations of naproxen with amorphous hydroxypropyl derivatives of α-, β-, and γ-cyclodextrin with an average substitution degree per anhydroglucose unit of 0.6 were investigated for thermal behaviour (differential scanning calorimetry), drug crystallinity (X-ray diffractometry), and dissolution rate (dispersed amount and rotating disc methods). Phase-solubility analysis and computer-aided molecular modelling were carried out to study the inclusion complexation of naproxen with hydroxypropyl cyclodextrins. The cavity size of the host is a selective factor for the solubilizing effect, complexing ability, and dissolution rate enhancement on naproxen, hydroxypropyl β-cyclodextrin being markedly the most effective derivative. No relationship was found between the decrease in crystallinity of the drug dispersed in the amorphous carrier matrix and the geometrical features of the cyclodextrin macrocycle.

Interaction of naproxen with β-cyclodextrin in solution and in the solid state

The behaviour of the inclusion complex of naproxen with β-cyclodextrin was studied by molecular modelling using interactive computer graphics, solubility diagrams at different temperatures and pH values, infrared spectroscopy and differential scanning calorimetry. The complex was prepared by freeze-drying, spray-drying and kneading. Three-dimensional modelling shows that naproxen lies totally enclosed in the interior of the β-cyclodextrin cavity. The energy calculated for the model indicates a high stability. The dependency of the stability in solution on pH and temperature, and the thermodynamic parameters calculated show the possible existence of intermolecular hydrogen bonds that are less stable with increasing pH. Infrared spectra show a shift to lower wavenumber in the carbonyl-stretching bands of naproxen for the products prepared by freeze-drying and spray-drying. This may be due to the formation of hydrogen bonds between the host and guest. Thermal analysis confirmed that freeze-drying and spray-drying led to complex formation. The kneading method, however, gives poor drug complexation; only one-third of the naproxen penetrates the cyclodextrin cavity, the rest remaining freely dispersed between uncomplexed host and inclusion compound.

Macromolecular prodrugs interaction with mixed lipid membrane. A calorimetric study of naproxen linked to polyaspartamide interacting with phosphatidylcholine and phosphatidylcholine-phosphatidic acid vesicles

The thermal behaviour of pure dipalmitoylphosphatidylcholine (DPPC) liposomes or mixed liposomes of DPPC with charged dipalmitoylphosphatidic acid (DPPA) and interacting with polymeric prodrugs has been investigated by differential scanning calorimetry (DSC). The apolar drug was naproxen (NAP) covalently linked to a water-soluble polymer (α,β- poly(N- hydroxyethyl)- dl - aspartamide (PHEA)). Addition of increasing amounts of NAP to DPPC liposomes causes a decrease in the transition temperature if( T m) associated to the gel-to-liquid crystal phase transition with a small decrease in the enthalpy values ( ΔH), whereas a corresponding amount of drug contained in the PHEA-adduct modifies the liposome phase transition by decreasing the ΔH and broadening the peak without T m variations. These effects have been interpreted as a different interaction of free or polymer-bound drug with the lipid bilayer. The drug effect on mixed liposomes was also investigated, and evidence of improved interaction of the drug-PHEA adduct with two-component bilayers, which better mimic biological membranes, was found. In order to understand the prodrug-lipid interactions, we modulated the surface charge density of the mixed liposomes with Ca 2+, which binds strongly to the negatively charged lipid head groups. We observed lateral phase separation, induced by NAP-PHEA adduct and modulated by Ca 2+, and the phenomenon was explained in terms of different drug solubility in DPPC-poor and DPPC-rich microdomains. The results are indicative of different interactions of naproxen, either free or bound to a polymeric carrier, with phospholipid membranes and the ability of Ca 2+ to influence the adsorption of the drug.

Binding of naproxen to bovine serum albumin and tryptophan-modified bovine serum albumin

Two classes of binding sites, a single high-affinity site with an association constant of 4·8×106 M−1 and two low-affinity sites with association constant of about 0·05×106 M−1 have been observed in the interaction of Naproxen with bovine serum albumin (BSA). Chemical modification of two tryptophan residues in BSA with 2-hydroxy-5-nitrobenzyl bromide has led to a reduction in the association constant of the high-affinity site by 89% and its number of binding sites by 66% suggesting the involvement of tryptophan residues in the high-affinity site. In contrast, the two low-affinity sites were not affected by the modification. Binding of Naproxen to the low-affinity sites of BSA induces microdisorganisation of the albumin structure leading to conformational changes as evident from fluorescence measurements with 1-anilino-8-naphthalenesulphonic acid as the probe.

Interaction of naproxen with cholestyramine.

'In vitro' and 'in vivo' studies were used to determine the interaction of naproxen, an anti-inflammatory agent, and cholestyramine, a hypocholesterolemic substance. Cholestyramine shows a marked affinity for naproxen and the intensity of this is governed by the pH values. The maximum amount of naproxen adsorbed by the resin is close to 2.2 mM g-1. The pharmacokinetics of naproxen was studied in eight healthy volunteers after concurrent oral administration in a single dose of 250 mg of naproxen and 4 g of cholestyramine. The resin causes an important delay in the incorporation of naproxen into the systemic circulation, though no significant modifications are seen to take place in any other pharmacokinetic parameters of the drug.