Diclofenac confirmation

Many studies have confirmed a complete biodegradation of ibuprofen to hydroxy-ibuprofen and carboxy-ibuprofen in biological wastewater treatment, whereas removals higher than 95% have been reached [17,49,50]. For diclofenac, contradictory results have been reported for its removal during CAS wastewater treatment. In some WWTPs, attenuation of 50-70% of diclofenac was reported [6, 10, 11, 51, 52], whereas some smdies showed extremely low efficiency of conventional treatment (only 10-30% removal) [49, 53]. 

The well known, beneficial influence of non-steroidal anti-inflammatory drugs (NSAID) on the progress of Alzheimer s disease has been confirmed for some NSAID subtypes. The work by Weggen et al. indicates the potential of COX 1 inhibitors (e.g. Diclofenac, Sulindac, Indomethacin, Ibuprofen, but not the most prominent, Aspirin) in PS inhibition [17]. 

Shinozuka et al. [91] developed a sensitive method for the determination of four anthranilic acid derivatives (diclofenac sodium, aluminium flufenamate, mefenamic and tolfenamic acids) by HPLC procedure. The four drugs were converted into methylphthalimide (MPI) derivatives in a constant yield by reaction with /V-chloromethylphthalimide at 60°C for 30 min. The production of the MPI derivatives were confirmed by mass spectrometry. The MPI derivatives of the four drugs were separated by HPLC using a C-18 bonded phase LiChrospher RP-18 column (250 x 4 mm i.d.) with acetonitrile-water (80 20, v/v) as mobile phase. The flow rate was 0.8 mL/min. The UV absorbance was measured at 282 nm. The calibration curves of the MPI derivatives of the drugs were linear from 1.0 to 5.0 pg/rnL. The detection limits of the four drugs were 0.5-5 ng. The extraction procedure for the four anthranilic acid derivatives added in the plasma and urine was performed by using Extrelut 1 column. Yields of column extraction of 100 pL of plasma and urine samples (containing 0.5 pg of anthranilic acid derivatives) with 6 mL of ethyl acetate were 84-106%. 

The more recent case-control study is that reported by Huerta et al [34A] using the General Practice Research Database from the United Kingdom. They confirmed that current use of NSAID increased the relative risk of AKI by 3.2 fold over non-users. They also identified significant increase in the relative risk of AKI when NSAID were combined with either diuretics (RR 11.6 (CL g 4.2-32.2)) or calcium channel blockers (RR 7.8 (3.0-20.5)). In addition, they provided analysis of individual NSAID relative risk. Diclofenac... 

The pharmacokinetic study involving diclofenac was designed to identify whether Ginkgo biloba exerted an inhibitory effect on cytochrome P450 isoenzyme CYP2C9, which is involved in the metabolism of diclofenac. Although an indication that such an effect may occur was noted in studies in vitro using S-warfarin, the in vivo study did not confirm that this interaction would be seen clinically. ... 

Although this interaction perhaps requires confirmation in a multiple-dose study in a clinical setting, the findings in healthy subjects suggest that no special precautions are required during the concurrent use of diclofenac and codeine. 

Shainhouse JZ, Grierson LM, Naseer Z. A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee. Am J Ther 2010 17(6) 566-76. 

Diclofenac and six metabolites (e.g., hydroxydiclofenac, dihydroxydiclofenac sul te, 4-amino-3,5-dichlorobenzene sulfonic acid) were isolated fi om urine and separated on a C, column ( = 282 nm). A 95/5 40/60 (at 20min) - 0/100 (at 22 min hold 4 min) water (10 mM ammonium formate at pH 7.0)/methanol gradient gave excellent separation. Time-of-flight MS was used to confirm peak identity [496]. 

A lower gastrointestinal risk with coxibs was confirmed in a retrospective case-control study of the incidence of peptic ulcer bleeding and perforation in users of COX-2 selective and non-selective NSAIDs [3 ]. The study was based on 2.2 million adults taking celecoxib, diclofenac, ibuprofen, naproxen, rofecoxib, or valdecoxib. Adjusted odds ratios (OR) compared with naproxen were ibuprofen 0.86 (95% Cl = 0.68, 1.09), rofecoxib 0.79 (0.62, 1.02), diclofenac 0.66 (0.47, 0.94), valdecoxib 0.50 (0.26, 0.97), and celecoxib 0.45 (0.35, 0.58). The overall... 

A study in 23 504 patients with osteoarthritis or rheumatoid arthritis, the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) study, confirmed lower gastrointestinal/liver adverse event discontinuation rates for etoricoxib versus diclofenac the hazard ratios (HR) were 0.46 (95% Cl =0.39, 0.54), 0.52 (0.42, 0.63), and 0.49 (0.39, 0.62) for etoricoxib 60 mg/day versus diclofenac 150 mg/day in osteoarthritis, etoricoxib 90 mg/day versus diclofenac 150 mg/day in osteoarthritis, and etoricoxib 90 mg/day versus diclofenac 150 mgiday in rheumatoid arthritis respectively [6 ]. 

---