The transsynovial distribution and tissue accumulation of tiaprofenic acid (Surgam)--a nonsteroidal anti-inflammatory agent--was studied in 55 patients scheduled for knee joint surgery. The patients suffering from rheumatoid arthritis (53), ankylosing spondylitis (1) or a chronicly irritated knee joint (1), received 300 mg of tiaprofenic acid b.i.d. starting 4 days prior to surgery. Samples of plasma, synovial fluid, fat, muscle, bone and synovial tissue were obtained simultaneously at defined times following the last dose. The samples were analyzed for tiaprofenic acid employing HPLC. Peak plasma concentrations of 28.6 micrograms/ml were achieved after 1 h, whereas synovial levels rose up to 2.8 micrograms/ml after 8 h. The time course of the concentration ratios indicates equilibration of both compartments 6 h following the last dose. Elimination occurs with half-lives of 1.9 h from plasma and 3.1 h from synovial fluid. During this period, synovial levels persist in a range sufficient for in vitro cyclooxygenase inhibition. In contrast, tiaprofenic acid does not exert marked tissue affinity, probably due to its hydrophilic properties.

Adult↗

PubMedDate not supplied

[Pharmacokinetics and biological availability of diclofenac preparations following intramuscular injection of 75 mg and oral administration of 150 mg of active drug].

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.

Administration, Oral↗