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Most affinity studies in capillary electrophoresis assume that the analyte concentration is much smaller than the additive concentration so that the migration of the analyte has no effect on the concentration of the additive in the capillary. However, in most medium- to high-affinity interactions, the additive concentration has to be kept rather low to observe the changes in analyte mobility before saturation is reached. In this paper, a mathematical model is developed to describe the migration behavior of the analyte in a system where the complex formed becomes concentrated to levels much greater than the original concentration of the additive due to the differences in the mobilities of the analyte, additive, and complex. The analyte is flurbiprofen, the additive is transthyretin, and the stoichiometry of the reaction between the two is 1:2. This study also provides a new algorithm to determine medium- to high-affinity binding interaction constants by CE.

Nitric oxide (NO) deficiency has been implicated in many pathological and physiological processes within the mammalian body providing a plausible biologic basis for the use of NO replacement therapy in these conditions. Exogenous NO sources may hopefully constitute a powerful way to supplement NO when the body cannot generate enough for normal biological functions. This theory has opened up the possibility of designing new drugs that are capable of delivering NO into tissues and the bloodstream in a sustained and controlled manner. This objective has been reached by grafting an organic nitrate structure onto existing molecules with various spacers such as aliphatic or aromatic chain, with different degree of complexity. This approach has led to the synthesis of several new chemical entities in various pharmacological classes, whose profile seems to challenge the parent drug not only on the basis of new pharmacological properties but also on a better toxicological and safety profile. In this article, general aspects on NO and NO donors are reviewed. Major focus is placed upon recent developments of novel NO donors, NO releasing device(s) as well as innovative improvements to conventional NO donors. Several examples are given in some important therapeutic indications such as cardiovascular diseases (NO-aspirin), pain and inflammation (NO-paracetamol), osteoporosis and urinary incontinence (NO flurbiprofen with aliphatic spacer), Alzheimers disease (NO-flurbiprofen with anti-oxidant spacer), respiratory disorders (NO-steroids).

Objectives: Determine whether recent US adverse event reports for several nonsteroidal anti-inflammatory drugs (NSAIDs) conform to the temporal pattern observed by Dr JCP Weber in the UK in the early 1980s, i.e. a rising count in the first few years after launch presumably reflecting increased exposure, followed by a decline, presumably reflecting decreased enthusiasm for reporting as adverse events become well known. Study Setting: US adverse event report data available from the US Food and Drug Administration, reformatted by a commercial vendor. Methods: For the 5 NSAIDs launched in the US between 1987 and 1993 that had data suitable for this study, we tabulated by year from launch the number of reports and the reporting rate (number of reports per 1000 prescriptions). Results: The number of reports for 3 of the 5 NSAIDs showed a temporal pattern approximating that described by Weber. The number of reports for the other 2 NSAIDs showed temporal patterns markedly different from that described by Weber. For 4 of the 5 NSAIDs, reporting rates did not decline consistently with time from launch. Discussion: The temporal patterns of adverse event reports are more complex than those described in Weber’s classic report. The number of reports does not reliably rise and then fall after launch and the reporting rate does not reliably decrease with time from launch.

In this study a complex of flurbiprofen and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD), was prepared employing a freeze-drying method. The production parameters and the final specifications of this product were optimised by using response surface methodology. The results show that the freeze-dried complex meets the requirements for solubility to be considered as a possible injectable form.

A new macrocyclic antibiotic, LY307599, has been evaluated as a chiral selector for the separation of the enantiomers of flurbiprofen using capillary electrophoresis (CE). The effect of varying separation buffer parameters such as buffer strength, pH, LY307599 concentration and methanol concentration were assessed. Using the optimized CE conditions, the separation of flurbiprofen enantiomers can be achieved using LY307599 as a chiral selector.

In der vorliegenden prospektiven, randomisierten und vergleichenden doppelt maskierten Studie wurde der entzundungshemmende Effekt von Diclofenac-0,1%- Flurbiprofen-0,03%- und Indomethacin- 1,0%-Augentropfen bei der postoperativen Behandlung nach Phakoemulsifikation mit Hinterkammerlinsenimplantation an 99 Patienten untersucht. Die Differenz zwischen den am 1. und am 4. bis 5. postoperativen Tag mit einem Laser-flare-Meter FM-500 (Fa. KOWA) gemessenen Flare-Werten in der Vorderkammer war in der Diclofenacgruppe signifikant groser als bei den mit Flurbiprofen behandelten Probanden (p = 0,022). Zusatzlich gaben die Patienten der Diclofenacgruppe verglichen mit Flurbiprofen und Indomethacin signifikant weniger Brennen und Stechen im Augenbereich an (4. bis 5. Tag: p

Purpose. A flexible microdialysis probe was designed for intravenous sampling in small laboratory animals.

Purpose. The in vivo plasma protein binding and pharmacokinetics of flurbiprofen were studied in awake, unrestrained rats using intravenous microdialysis sampling.

A single-centre, double-blind, single-dose study was conducted to assess the primary irritancy of a local action transcutaneous (LAT) patch preparation of flurbiprofen (Targus/TransAct LAT) when applied to the skin of 24 Caucasian volunteers. Comparisons were made of flurbiprofen LAT with non-medicated control, unperfumed moisture cream and a plain lint patch. It was found that the primary irritancy of the flurbiprofen LAT preparation was minimal. This finding, together with previous experience in Japanese subjects, suggests that skin irritancy is unlikely to be a prevalent adverse event when flurbiprofen LAT is used clinically in Caucasian patients.

A stability-indicating high-performance liquid chromatography method for the quantitation of flurbiprofen in tablets was developed. The method is accurate and precise with a percent relative standard deviation of 0.7 based on 8 readings. A number of inactive ingredients present in the tablets did not interfere with the assay procedure. The extraction procedure from the tablets is very simple. The recovery from the synthetic mixtures was quantitative. The drug appears to be very sensitive to strong acids and bases since a 5 minute boiling caused the degradation of drug (100 %) in both the solutions

Indometacin is well known as local eye drug for the prevention of cystoid macular oedema. The concentration is 50mg/5ml. Another inhibitor of the prostaglandin synthesis is flurbiprofen; its concentration is 1.5mg/5ml. Indometacin is a suspension and available in different concentrations dependent on the shaking procedure. We measured the concentration of indometacin in one single eyedrop from a full bottle, half full and a nearly empty bottle. After correct shaking the concentration of indometacin was between 48 and 53mg/5ml.

In a prospective randomised study we tested two non-steroidal anti-inflammatory medications clinically in a group of 40 eyes. 20 eyes received topically administered indometacin and another 20 flurbiprofen eyedrops. Before we started the planned extracapsular cataract extraction we performed a puncture of the anterior chamber and aspirated a small volume of anterior chamber fluid. We examined the concentrations of the applied drugs in the aspirated volume. The concentration of indometacin is 7–9 times higher than that of flurbiprofen.

In a prospective, randomized double-blind study, the anti-inflammatoy effects of indomethacin and flurbiprofen were examined. The operation performed was extracapsular cataract extraction. For the pre

Based on an investigation on furbiprofen solubilization in polysorbate 80 solutions at different pH, this study proposed an equilibrium-based model to characterize the drug–surfactant interactions in pH controlled system. The model reflected both interactions and interdependence among all drug-containing species: unionized drug in water D u , ionized drug in water D i , unionized drug in micelles D u M , and ionized drug in micelles D i M . The micelles were defined and quantitated as the micellized surfactants, so both D u M and D i M were also seen as unionized and ionized drug associated with micellized surfactants. This mathematical treatment enables the modeling of the drug solubilization in pH-surfactant solutions without making unsound approximations. Using a separate set of solubility data at a different pH, a comparison was conducted between experimental data and the solubility estimated by this model, and by the partition model proposed by Rippie et al. It was found that both models yielded reasonably good estimation compared with experimental data. It was also found that the solubility data estimated by the proposed model were more reliable especially when the surfactant concentration was high in the system. This suggests that the consideration of interrelations and interdependence of all drug species in pH-surfactant solutions by this model is justified and appropriate.

The buccal absorption of flurbiprofen was evaluated in nine normal volunteers. Twenty milliliters of 2.5 mg/ml flurbiprofen solution (pH 8.03) was administered as a 1-min mouthwash or a 5-min mouthwash or swallowed. Serum was harvested from blood samples taken at specified times over a 12-hr period. Serum flurbiprofen concentration data indicate that the extent, but not the rate, of drug absorption was dependent upon the time of exposure of the flurbiprofen solution to the buccal membrane. Following the 1- and 5-min mouthwash treatments, 5.2 and 9.4% of the administered doses were absorbed, respectively.

We report a case of biopsy-proven acute tubulointerstitial nephritis associated with a second course of flurbiprofen, a nonsteroidal anti-inflammatory drug of the propionic acid class. The clinical presentation and course was consistent with acute tubulointerstitial nephritis due to these agents.

Flurbiprofen Na and diclofenac Na, two ocular antiinflammatory agents, were investigated to determine the aqueous humor concentrations in the human eye following topical application. One hundred sixty-five patients undergoing cataract surgery received a single drop of either diclofenac Na or flurbiprofen Na at selected times prior to the surgical procedure. Aqueous humor samples were aspirated at the beginning of surgery and a sensitive high-performance liquid chromatographic assay was used to determine the concentration of the antiinflammatory agent in the ocular fluid. Samples were obtained between 10 min and 24 hrs after a single instillation of the drug onto the cornea. The highest average concentration of diclofenac was 82 ng/ml at 2.4 hrs after instillation; concentrations remained above 20 ng/ml for over 4 hrs. Thereafter, between 3 and 16 ng/ml diclofenac could be assayed through 24 hrs. The highest average concentration of flurbiprofen, 60 ng/ml, was found at 2.0 hrs. The last detectable flurbiprofen concentration was measured at 7.25 hrs after instillation.

In order to evaluate the anti-inflammatory effect of non-steroidal compounds on the eye, we tested them in rabbits using the inhibitory effect on paracentesis-induced disruption of the blood-aqueous barrier. Protein and--after intravenous-injection--fluorescein were determined in punctates of aqueous humor. Indomethacin, flurbiprofen and diclofenac in a 0.01% solution showed a marked inhibitory effect, which lasted for 24 h. Addition of polysorbate to eye drugs diminished the inhibitory effect.

Fifty male children, aged between 3 and 10 years, were treated for a 12-day period with either trimethoprim (80–160 mg) plus sulphamethoxazole (400–800 mg) daily (co-trimoxazole) or 50–125 mglday flurbiprofen rectally. The patients had been treated surgically for criptorchidism. Flurbiprofen showed good effectivity in controlling post-operative inflammation in urology. It is concluded that antimicrobial agents such as co-trimoxazole, because of their potential risks of damage at the cell's level, should be used only in presence of a bacterial infection.

• The ocular bioavailability of radiolabeled flurbiprofen was determined after single or multiple topical dosing of rabbits. Three doses at half-hour intervals of a 0.03% solution produced higher concentrations in the tissues than those after a single dose of either the 0.03% or the 0.1% solution. Three doses of 0.03% flurbiprofen gave intraocular concentrations in the range that inhibits cyclo-oxygenase activity. Administration of more than three doses did not significantly increase the concentration of flurbiprofen in most tissues. The drug distribution pattern in the ocular tissues after multiple dosing was the same as after single dosing. Although multiple dosing with the 0.03% concentration resulted in higher tissue levels of flurbiprofen, increasing the concentration to 0.1% did not result in greater ocular bioavailability of the drug.