Bioavailability of diclofenac potassium at low doses

Abstract

Br J Clin PharmacolAim 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. MethodsA 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. ResultsMean ( ± 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%). ConclusionsOur 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.

Pharmacokinetics of diclofenac in rats intoxicated with CCL4, and in the regenerating liver

“…Diclofenac is a medium hepatic extraction ratio drug [16] and undergoes considerable first-pass metabolism. Therefore, its oral bioavailability is importantly affected [2,6,46,47].…”

“…It is eliminated principally by hepatic metabolism, and has analgesic, antipyretic, and anti-inflammatory properties in animals and man, making it useful in the treatment of rheumatoid arthritis, osteoarthritis [2], ankylosis and pain of varying origin, and thus treatment is not discontinued even if liver damage is present [3][4][5]. Due to the central role of the liver in the overall elimination of the majority of NSAIDs, hepatic diseases will most likely lead to a significant alteration in their pharmacokinetic behavior [6].…”

Anti-inflammatory Activity of Methanolic Extract from Pistacia atlantica Desf. Leaves

“…The rapid anti-inflammatory effect of Diclofenac is due to its pharmacokinetic properties represented by a 1h Tmax and a bioavailability of 65% with oral administration. 34 The later action of the MEPaL could be explained both by the pharmacokinetic and pharmacodynamic behaviour of the active secondary metabolites. Indeed, the digestion and absorption of flavonoids are slow processes especially for glycosylated forms because of the resistance of the osidic bonds resulting in decrease of bioavailability.…”

Development and Validation of a Bioanalytical Method for Direct Extraction of Diclofenac Potassium from Spiked Plasma

“…It has a single dissociation constant (pKa) of 4.0 ± 0.2 at 25°C in water [1]. Diclofenac potassium (Diclo-K) is a substituted phenyl-acetic acid derivative and widely used in the management of many inflammatory conditions [2][3]. It also has analgesic and antipyretic actions.…”

“…However, analysis of analytes present in matrices such as plasma requires welldesigned sample preparation procedures such as protein precipitation, centrifugation, extraction and filtration that can introduce experimental errors and ultimately reduce precision and accuracy of measurement [3][4]. An attractive approach would be to reduce the number of treatments in sample preparation procedure in order to minimize human and non-human errors.…”