Comparative bioavailability of two different diclofenac formulations in healthy volunteers.
ABSTRACT The aim of the study was to assess the bioequivalence of two different diclofenac (CAS 15307-86-5) formulations (diclofenac free acid suspension as test formulation and diclofenac resinate suspension, Cataflam, as reference formulation) in 24 healthy volunteers. After an overnight fast, the volunteers received a single oral dose (50 mg) of each formulation, following an open, randomized, two-period crossover design, with a fourteen-day washout interval between doses. Serum samples were obtained over a 24-h interval post-dosing, and were analysed for their diclofenac content by HPLC-UV. No adverse effect was reported for any of the formulations administered. Geometric mean test/reference individual ratios were: 92.8% for AUC(0-24 h), 93.2% for AUC(0-infinity), 117.2% for Cmax, 131.0% for Ke and 76.2% for T1/2. The variability of Cmax parameter expressed as CV was greater than 25%. Since the 90% CI for AUC(0-24 h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for the extent of absorption. Since the European Community Agency accepts a 90% CI for Cmax of 70-143%, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for both the rate and the extent of absorption after single dose administration.
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ABSTRACT: Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) widely prescribed for pain and inflammation. Theoretically, the gastrointestinal (GI) complications of diclofenac could be minimized by administering a diclofenac resinate formulation, such as Flotac, where GI mucosal contact with free NSAID is minimized by its complexing with the cholestyramine resin. The objective of the present study was to investigate the influence of cholestyramine co-treatment on diclofenac enteropathy in fed rats and diclofenac gastropathy in fasted rats. Male Sprague-Dawley rats were gavaged with diclofenac (50 mg/kg), diclofenac (50 mg/kg) plus cholestyramine (50 mg/kg), or an equivalent amount of Flotac, a 1:1 wt/wt mixture of diclofenac and cholestyramine presently used in human therapeutics in Mexico. Ulceration of the GI tract, serum proteins, and bile salts were assessed at 3, 12, or 24 h. Cholestyramine alone produced no detectable alterations in small intestinal integrity or serum bile salts levels. Fed rats given Flotac or diclofenac plus cholestyramine showed patterns of small intestinal ulceration and serum protein decline that were similar to rats given only diclofenac. Thus, no influence on enteropathy was detected. In contrast, fasted rats given Flotac showed a modest reduction in the number and length of gastric lesions compared to rats given diclofenac. The observed attenuation of gastric lesions with Flotac is consistent with a role for direct cytotoxicity in NSAID gastropathy. Drug Dev. Res. 64:19–27, 2005. © 2005 Wiley-Liss, Inc.Drug Development Research 12/2004; 64(1):19 - 27. DOI:10.1002/ddr.10417 · 0.73 Impact Factor
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ABSTRACT: The clinical utility of diclofenac potassium, a nonsteroidal anti-inflammatory drug, may be lessened by inconsistent gastrointestinal absorption. Diclofenac potassium liquid filled soft-gelatin capsule (DPSGC) is an investigational formulation that uses ProSorb dispersion technology to facilitate rapid and consistent gastrointestinal absorption. In this study, the pharmacokinetic (PK) properties of DPSGC are investigated and compared with a commercially available oral diclofenac potassium tablet in patients after primary unilateral first metatarsal bunionectomy. In an open-label, randomized study, 53 patients received ProSorb-D 12.5 mg (the liquid equivalent of DPSGC), DPSGC 25 mg, DPSGC 50 mg, or immediate-release diclofenac potassium 50-mg tablet administered every 8 hours for a 24-hour inpatient period followed by 7 days of outpatient dosing. Diclofenac steady-state PK was evaluated over an 8-hour sampling period 4 days after surgery. Delayed and/or multiple peaks in the diclofenac plasma concentration-time course profiles occurred more frequently with the commercially available oral diclofenac potassium 50-mg tablet than with the other DPSGC formulations. PK data for ProSorb-D 12.5-mg liquid, DPSGC 25 mg, DPSGC 50 mg, and diclofenac potassium 50-mg tablet revealed mean peak plasma concentrations (Cmax) of 302, 749, 1006, and 902 ng/mL, respectively, whereas area under the plasma concentration curve values were 316, 595, 1029, and 1166 ng-hour/mL, respectively. Mean times to Cmax (tmax) were 0.49, 0.63, 0.95, and 1.26 h, respectively. When compared with absorption characteristics of diclofenac potassium 50-mg tablet, DPSGC was more rapidly and consistently absorbed after bunionectomy. These characteristics should be advantageous when rapid pain relief is desired.American journal of therapeutics 07/2009; 17(5):460-8. DOI:10.1097/MJT.0b013e3181aa3eda · 1.13 Impact Factor