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Bioavailability of diclofenac potassium at low doses
Author(s) -
Hinz Burkhard,
Chevts Julia,
Renner Bertold,
Wuttke Henrike,
Rau Thomas,
Schmidt Andreas,
Szelenyi Istvan,
Brune Kay,
Werner Ulrike
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02226.x
Subject(s) - diclofenac , bioavailability , bioequivalence , confidence interval , pharmacokinetics , pharmacology , oral administration , medicine , absorption (acoustics) , chemistry , physics , acoustics
Aim Diclofenac‐K has been recently launched at low oral doses in different countries for over‐the‐counter use. However, given the considerable first‐pass metabolism of diclofenac, the degree of absorption of diclofenac‐K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low‐dose diclofenac‐K. Methods A randomized, three‐way, cross‐over study was performed in 10 subjects. Each received diclofenac‐K, 22.5 mg via short‐term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration ( t max ) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac‐K after oral administration did not differ significantly in the 12.5‐mg and 25‐mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC ∞ and AUC t ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac‐K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton‐time curve; C max , peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F , absolute bioavailability; t max , time to reach C max .