Bioavailability of diclofenac potassium at low doses.
OBJECTIVE
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(infinity) 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 concentration-time curve; C(max), peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; t(max), time to reach C(max).
Hinz
Burkhard
B
Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany. hinz@pharmakologie.uni-erlangen.de
Chevts
Julia
J
Renner
Bertold
B
Wuttke
Henrike
H
Rau
Thomas
T
Schmidt
Andreas
A
Szelenyi
Istvan
I
Brune
Kay
K
Werner
Ulrike
U
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac