OBJECTIVES:

To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs.

METHODS:

Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance.

RESULTS:

A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment.

CONCLUSIONS:

Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

A fourteen-month monitoring period (April 2007-May 2008) was realized to investigate the removal and occurrence of eight pharmaceutical and personal care compounds, two metabolites and caffeine across the municipal wastewater treatment plant (WWTP) of Agrinio city, located in Western Greece as well as in the discharging sampling point in Acheloos River, which receives the effluents of the plant. Solid-phase extraction (SPE) was used for the isolation and pre-concentration of the target pollutants and gas chromatography mass spectrometry (GC-MS) for their detection and quantification. All the selected compounds were detected in the wastewater samples. The concentrations determined in the influent of the municipal WWTP ranged between 65.3 and 6679 ng L(-1) recorded for triclosan and caffeine respectively, while in the effluent ranged between 24.9 and 552 ng L(-1) observed for triclosan and carbamazepine, respectively. The detected concentration levels in Acheloos River ranged from 37.6 ng L(-1) for caffeine to 305 ng L(-1) for paracetamol. Mean total removal efficiencies ranged between 46.3% for carbamazepine and 96.8% for naproxen. The results of this study demonstrate that most of the compounds are being reduced in low levels by municipal wastewater treatment processes but quite significant levels of pharmaceuticals enter river waterways.

The UVB component of sunlight, which causes DNA damage and inflammation, is the major cause of nonmelanoma skin cancer (NMSC), the most prevalent of all cancers. Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs have been shown to be effective chemoprevention agents in multiple preclinical trials, including NMSC, colon and urinary bladder cancer. NSAIDs, however, cause gastrointestinal irritation, which led to the recent development of nitric oxide (NO) derivatives that may partially ameliorate this toxicity. This study compared the efficacy of several NSAIDs and NO-NSAIDs on UV-induced NMSC in SKH-1 hairless mice and determined whether various short-term biomarkers were predictive of long-term tumor outcome with these agents. Naproxen at 100 (p>.05) and 400 ppm (p<.01) in the diet reduced tumor multiplicity by 26 and 63% respectively. The NO-naproxen at slightly lower molar doses shows similar activities. Aspirin at 60 or 750 ppm in the diet reduced tumor multiplicity by 19 and 50%; while the equivalent doses (108 and 1350 ppm) were slightly less effective. Sulindac at 25 and 150 ppm in the diet doses far below the Human Equivalent Dose, was the most potent NSAID with reductions of 50 and 94% respectively. In testing short-term biomarkers we found that agents that reduce UV-induced prostaglandin E2 synthesis and/or inhibit UV-induced keratinocyte proliferation yielded long-term tumor efficacy.

Quantitative information regarding the capacity of rivers to self-purify pharmaceutical residues is limited. To bridge this knowledge gap, we present a methodology for quantifying the governing processes affecting the fate of pharmaceuticals in streaming waters and, especially, to evaluate their relative significance for tracer observations. A tracer test in Säva Brook, Sweden was evaluated using a coupled physical-biogeochemical model framework containing surface water transport together with a representation of transient storage in slow/immobile zones of the stream, which are presumably important for the retention and attenuation of pharmaceuticals. To assess the key processes affecting the environmental fate of the compounds, we linked the uncertainty estimates of the reaction rate coefficients to the relative influence of transformation and sorption that occurred in different stream environments. The hydrological and biogeochemical contributions to the fate of the pharmaceuticals were decoupled, and the results indicate a moderate hydrological retention in the hyporheic zone as well as in the densely vegetated parts of the stream. Biogeochemical reactions in these transient storage zones further affected the fate of the pharmaceuticals, and we found that sorption was the key process for bezafibrate, metoprolol, and naproxen, while primary transformation was the most important process for clofibric acid and ibuprofen. Conversely, diclofenac was not affected by sorption or transformation.

An analytical method has been developed and validated for the simultaneous determination of 18 pharmaceuticals and personal care products (PPCPs), including antibiotics (trimethoprim, erythromycin x 2H2O, norfloxacin, ofloxacin, pencilline G, penicillin V potassium salt, cephalexin and sulfamethoxazole), beta-bloker (atenolol), anophelifuge (N, N-diethyl-3-methylbenzoylamide, DEET), antiepileptics (carbamazepine), central nervous system stimulant (caffeine), lipid modifying agent (clofibric acid), non-steroidal anti-inflammatory drugs (ibuprofen, naproxen and diclofenac sodium salt) and antimicrobial agents (triclosan and triclocarban). The detection and qualification of the target compounds were performed by ultra-high performance liquid chromatography-tandem mass spectrometry. The optimized mobile phases were methanol as organic phase, 0. 3% (v/v) formic acid-5 mmol/L ammonium acetate for positive electrospray ionization (ESI+) and 5 mmol/L ammonium acetate for ESI- as inorganic phase. Water samples were concentrated by solid phase extraction at 2 mL/min, and all the target PPCPs were efficiently extracted at pH 7. The extracted PPCPs were eluted by the mixture of methanol and acetonitrile (1 : 1, v/v). The average recoveries of the target compounds in the spiked pure water samples ranged from 53.9% - 112%. The average recoveries of the target compounds ranged from 45.1% - 156.6% with the relative standard deviations ranged from 2.4% - 15.7%, in the surface water samples spiked at 100 ng/L. The surface water samples collected from Yu Hangtang River in Hangzhou were detected. The results showed that nine PPCPs were detected including caffeine that reached a maximum concentration of 550.7 ng/L. It proved that this analytical method is reliable and acceptable.

BACKGROUND:

In the UK, over 90 medicines that were previously available only through prescription have been reclassified to allow over-the-counter (OTC) availability via pharmacies. Pharmacists are personally responsible for undertaking or supervising the sales and supplies of these OTC 'pharmacy only' (P) medicines. Reclassification facilitates pharmacy management of a wide range of conditions.

OBJECTIVE:

This research aimed to evaluate Scottish community pharmacists' perspectives of newly reclassified 'P' medicines from diverse therapeutic areas and to identify factors associated with their adoption into practice of these medicines.

METHODS:

A cross-sectional postal survey of all community pharmacies in Scotland (N = 1138) was undertaken. The questionnaire was mailed to the pharmacist responsible for OTC medicines. Four newly reclassified 'P' medicines: omeprazole, naproxen, simvastatin and chloramphenicol eye drops were evaluated. Outcomes of interests included pharmacist support for the reclassified status, perceived adoption into practice of these medicines (i.e., how often they supplied each of these medicines) and factors associated with decision-making. Analyses included descriptive, bivariate correlation, principal component factor and binary regression.

RESULTS:

Five hundred sixty-three pharmacists responded (response rate: 49.5%). Newly reclassified medicines studied had been adopted into practice by the respondent pharmacists to varying degrees. A high majority of the respondents expressed support for the reclassified status (82.4%) and perceived that the level of adoption into practice of OTC chloramphenicol was high (92.1%). In contrast, over 80% of respondents had not yet made a supply of OTC simvastatin to patients, mainly owing to pharmacists' perceptions of lack of evidence of efficacy of the OTC dose and patient demand. Decision-making was influenced by factors such as perceived benefits to patients and pharmacy practice; e.g., respondents who agreed that reclassified naproxen was a good opportunity to develop their professional role were significantly more likely to rate their support for the reclassified status highly than those who were unsure or disagreed (odds ratio = 3.7 (95% confidence interval: 2.1-6.7); P value <0.001).

CONCLUSIONS:

Key factors informing decisions to adopt the reclassified medicines into pharmacists' practice relate to perceptions regarding the benefits of reclassification to patient care and their professional roles. The results have relevance to future reclassification decisions.

The metal-organic framework MIL-101 was fabricated in a polyetheretherketone (PEEK) tube as micro-trapping device, and applied to sorptive extraction of naproxen and its metabolite in urine samples. The remarkable water stability of the MIL-101 characterizes the material as being different from other moisture sensitive metal-organic framework. It is therefore suitable for extraction of pharmaceuticals from biological fluids. The adsorption isotherms in aqueous solution showed that the adsorption of naproxen on MIL-101 is endothermic. Additionally, MIL-101 exhibited higher extraction capacity to naproxen than that of C18-bonded silica and multi-walled nanotube. A specially designed in-tube sorptive extraction (ITSE) device endows the extraction process with the characteristic of rapidness, convenience, and easy of conjunction with high performance liquid chromatography (HPLC). Finally the MIL-101 based ITSE method coupled with HPLC and fluorescence detection was applied to analysis of naproxen and 6-O-desmethylnaproxen in urine samples. Parameters that influence the online extraction procedure, including pH of the sample solution, flow rate of extraction, sample volume, desorption solvents and time were investigated. The method is proved to be highly sensitive with the linear range of 0.05-6.0μgL(-1) and the limits of detection of 0.034 and 0.011μgL(-1) for naproxen and 6-O-desmethylnaproxen, respectively. The recoveries in urine samples were 85.3-98.3% for naproxen and 94.0-97.3% for 6-O-desmethylnaproxen with intra- and inter-day RSDs of 2.7-5.2% and 7.1-8.1%, respectively. Urine samples could be directly subjected to analysis without any additional sample pretreatment. The proposed method was demonstrated an efficient, flexible and versatile extraction tool which is ideally suitable for online conjunction with chromatographic methods.

The purpose of the present investigation was to prepare matrix tablets of naproxen using a hydrophobic polymer, i.e., Eudragit RLPO, RSPO, and combination of both, by wet granulation method. The tablets were further coated with different concentrations of Eudragit S-100, a pH-sensitive polymer, by dip immerse method. In vitro drug release studies of tablets were carried out in different dissolution media, i.e., 0.1 N HCl (pH 1.2), phosphate buffers pH 6.8 and 7.4, with or without rat cecal content. The swelling studies of the optimized formulation were carried out. The physicochemical parameters of all the formulations were found to be in compliance with the pharmacopoeial standards. The effect of dissolution medium on the surface of matrix tablet was determined by using Scanning Electron Microscopy technique. The stability studies of all formulations were performed as per ICH guidelines. The results demonstrated that the tablets coated with Eudragit S-100 (2% w/v) showed a sustained release of 94.67% for 24 h, but drug release increased to about 98.60% for 24 h in the presence of rat cecal content while the uncoated tablets released the drug within 5 h. With regard to release kinetics, the data were best fitted with the Higuchi model with non-Fickian drug release kinetics mechanism. The stability studies of tablets showed less degradation during accelerated and room temperature storage conditions for 6 months. The enteric-coated Eudragit S-100 coated matrix tablets of naproxen showed promising site-specific drug delivery in the colon region.

Pharmaceuticals and personal care products (PPCPs) have been documented throughout the United States freshwaters but research has focused largely on lotic systems. Because PPCPs are designed to have a physiological effect, it is likely that they may also influence aquatic organisms. Thus, PPCPs may negatively impact aquatic ecosystems. The objectives of this research were to quantify PPCP abundance in near-shore habitats of southern Lake Michigan and identify factors related to PPCP abundance. Stratified sampling was conducted seasonally at four southern Lake Michigan sites. All sites and depths had measurable PPCP concentrations, with mean individual compound concentrations of acetaminophen (5.36ng/L), caffeine (31.0ng/L), carbamazepine (2.23ng/L), cotinine (4.03ng/L), gemfibrozil (7.03ng/L), ibuprofen (7.88ng/L), lincomycin (4.28ng/L), naproxen (6.32ng/L), paraxanthine (1,7-dimethylxanthine; 46.2ng/L), sulfadimethoxine (0.94ng/L), sulfamerazine (0.92ng/L), sulfamethazine (0.92ng/L), sulfamethoxazole (26.0ng/L), sulfathiazole (0.92ng/L), triclocarban (5.72ng/L), trimethoprim (5.15ng/L), and tylosin (3.75ng/L). Concentrations of PPCPs varied significantly among sampling times and locations (river mouth vs offshore), with statistical interactions between the main effects of site and time as well as time and location. Concentrations of PPCPs did not differ with site or depth. Temperature, total carbon, total dissolved solids, dissolved oxygen, and ammonium concentrations were related to total pharmaceutical concentrations. These data indicate that PPCPs are ubiquitous and persistent in southern Lake Michigan, potentially posing harmful effects to aquatic organisms.