Z Rheumatol. 1988 Jan-Feb;47(1):37-42.

[Pharmacokinetics and biological availability of diclofenac preparations

following intramuscular injection of 75 mg and oral administration of 150
mg of active drug]

[Article in German]

Kurowski M.

Friedrich-Alexander-Universität Erlangen-Nürnberg, Institut für Pharmakologie

und Toxikologie.

Four different formulations of diclofenac sodium, a widely used NSAID, were

administered to eight healthy young volunteers in a cross-over study, according to
a latin-square design. The subjects received either 75 mg as intramuscular
injections or 150 mg as enteric-coated tablets. Following administration, blood
samples were drawn and analysed for unchanged diclofenac, employing HPLC.
72.9% of the oral dose was absorbed with an average lag-time of 2.2 h. Peak
plasma concentrations amounted to 2.9 micrograms/ml after 3.1 h, as compared to
2.15 micrograms/ml, 20-30 min following an intramuscular injection of 75 mg.
Diclofenac sodium was excreted with an average half-life of 1.15 h. The
bioavailability of the three i.m. injectable solutions, as calculated from the area
under the curve (AUC), did not differ significantly. The results suggest that i.m.
injectable diclofenac sodium provides fast drug liberation suitable for acute
analgesic treatment, although the general risk of i.m. injections, as well as the
very rare risk of protracted anaphylactic shocks, has to be taken into account.
Despite the high variability of absorption, peak plasma concentrations and
bioavailability, the enteric-coated tablets may be favourable in chronic
antiinflammatory therapy.

PMID: 3369245 [PubMed - indexed for MEDLINE]

Int J Clin Pharmacol Ther. 2005 Nov;43(11):546-50.

Bioequivalence of diclofenac injection formulations assessed in Korean

males.

Zhu X, Shin WG.

Clinical Pharmacy, College of Pharmacy, Seoul National University, South

Korea.

A bioequivalence study of diclofenac injection (test formulation (diclofenac

potassium): HANA, reference formulation (diclofenac sodium): Shinpoong) was
conducted in 18 healthy male Korean volunteers who received each medicine at a
dose of 75 mg in a 2 x 2 crossover study. There was a one-week washout period
between the doses. Plasma concentrations of diclofenac were monitored by high-
performance liquid chromatography over a period of 24 hours after the i.m.
injection. AUC0-24 (the area under the plasma concentration-time curve from
time 0-24 hours) was calculated by the linear-log trapezoidal method. Cmax
(maximum plasma drug concentration) and tmax (time to reach Cmax) were
compiled from the plasma concentration-time data. Analysis of variance was
carried out using logarithmically transformed AUC0-24 and Cmax, and non-
transformed tmax. There were no significant differences between the medications
in AUC0-24 and Cmax. The point estimates and 90% confidence intervals for
AUC0-24 (parametric) and Cmax (parametric) were 0.973 (0.8971 to 1.0557) and
0.993 (0.9452-1.0451), respectively, satisfying the bioequivalence criteria of the
European Committee for Proprietary Medicinal Products and the US Food and
Drug Administration Guidelines. The corresponding value for tmax was 0.75
(0.00 to 1.00). Moreover, the modified Pitman-Morgan's adjusted F-test indicated
that the bioavailabilities of diclofenac in the two medications were comparable
regarding intra- and interindividual variability. Therefore, these results indicate
that the two medications of diclofenac are bioequivalent and, thus, may be
prescribed interchangeably.

PMID: 16300171 [PubMed - indexed for MEDLINE]