title: [Relative bioavailability of diclofenac after a single administration of a new multiple-unit formulation of enteric-coated pellets].
abstract: The relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after a single administration of a multiple-unit formulation containing 75 mg diclofenac sodium in enteric-coated pellets (A) in comparison to an enteric-coated tablet with 50 mg diclofenac sodium (B), a capsule containing 140 mg diclofenac resinate (C) and a dispersible tablet containing 46.5 mg diclofenac acid (D). The study was carried out in a four-way crossover design in 16 healthy male volunteers. Serum concentrations of diclofenac were determined with a validated and specific HPLC-method. After dose normalisation, a mean relative bioavailability of 99% (B), 142% (C) and 116% (D) was determined for the pellet formulation. According to the corresponding 90%-confidence interval, bioequivalence for the extent of bioavailability of the test formulation can be concluded compared to the enteric-coated tablet. In comparison to the formulations C and D, the test formulation showed an increased extent of bioavailability. Further differences in pharmacokinetics were observed for the rate-dependent parameters. For the test formulation, the highest mean maximum serum concentration (1595 ng/ml) was measured with a corresponding tmax of 0.8 h. For the reference formulations, mean peak serum concentrations of 1285 ng/ml after 2.0 h (B), 370 ng/ml after 1.8 h (C) and 735 ng/ml after 1.9 h (D) were observed. Despite the enteric-coating of the pellets, a short lagtime of 0.4 h was determined for the test formulation. For the other rapid-release formulation (D), the lagtime was of a similar magnitude (0.3 h), while drug release and absorption from the enteric-coated tablet and the diclofenac resinate capsule were delayed (1.8 and 0.7 h, respectively). Due to the rapid and high bioavailability of diclofenac, the multiple-unit formulation fulfills the prerequisites for the oral treatment of acute painful conditions when prompt analgesic and anti-inflammatory efficacy is desired.
authors.affiliation: Klinge Pharma GmbH, München. kersten.walter@klinge-pharma.de
authors.forename: K
authors.initials: K
authors.lastname: Walter
authors.forename: A
authors.initials: A
authors.lastname: von Nieciecki
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004008:Diclofenac / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D013256:Steroids; D013608:Tablets, Enteric-Coated
chemical_list: D000893:Anti-Inflammatory Agents; D013256:Steroids; D013608:Tablets, Enteric-Coated; D004008:Diclofenac