Comparative bioavailability of two different diclofenac formulations in healthy volunteers

Department of Pharmacology, Campinas University, São Paulo, Brazil.
Arzneimittel-Forschung (Impact Factor: 0.7). 12/1999; 49(11):920-4. DOI: 10.1055/s-0031-1300527
Source: PubMed


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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    • "For example, in Mexico, more than 4% of diclofenac is prescribed as a formulation, notably Flotac [Adriana Rojas, personal communication], where this NSAID is complexed with cholestyramine, an ion exchange resin. Administration of this diclofenac-cholestyramine complex (Fig. 1) yielded a favorable rapid plasma level that would facilitate drug transfer to effect compartments [Kurowski et al., 1994; Silva et al., 1999; Castañ eda-Hernández et al., 2001]. Clinical comparison studies in patients with rheumatoid or osteoarthritis have found that the analgesic efficacy of Flotac is similar to an enteric release formulation or the sodium salt of diclofenac [Kurowski et al., 1994; Castañ eda-Hernández et al., 2001]. "
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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 · 0.77 Impact Factor
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    ABSTRACT: A novel high-performance liquid chromatographic (HPLC) method for the quantification of diclofenac in human plasma was set up. Samples, added with ibuprofen (used as internal standard) were purified by solid-phase extraction using Abselut Nexus cartridges (Varian) not requiring pre-conditioning. Drugs of interest were eluted directly into the autosampler vials and injected. The recovery of diclofenac was 92%, the analysis lasted 7 min with a sensitivity of 5 ng/ml and intra- and inter-day RSDs of 3 and 8%, respectively. The pharmacokinetics of diclofenac after oral and rectal administration in 10 healthy volunteers are reported.
    Journal of chromatography. B, Biomedical sciences and applications 12/2001; 763(1-2):195-200. DOI:10.1016/S0378-4347(01)00383-8
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    Proceedings of the Western Pharmacology Society 02/2002; 45:26-8.
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