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Abstract :
[en] Intra-articular injections of glucocorticoids aim to control pain and inflammation caused by osteoarthritis. There is a lack of evidence and pharmacokinetics (PK) studies to support the empirical currently used dosage regimens. This study aimed 1) to determine the PK of triamcinolone hexacetonide (TH) and triamcinolone acetonide, its active metabolite (TA), in synovial fluid after intra-articular administration of a suspension of TH at 40mg and 10mg in sheep and 2) to compare the profiles of TA after injection of suspensions of TA or TH, both at 40mg. Twelve sheep were randomly allocated to three groups receiving respectively 40 mg TA (n=4), 40 mg TH (n=4) or 10 mg TH (n=4) in the left knee. Synovial fluids were sampled from day 1 up to day 21. The concentrations of TA and TH were measured by ultra-performance liquid chromatography mass spectrometry. TA concentrations measured after one day were higher in the group TA-40 mg (537762.3ng/ml) compared to those recorded in the group TH-40mg (22743.4ng/ml), On day 21, the corresponding values were 2.5 and 33.5 ng/ml due to a significant higher value of T1/2β of TA in group TH-40 mg (6.0 versus 1.9 days). The differences between the mean values of AUC and T1/2β of TA were not significantly different between the groups TH-10 and -40 mg but T1/2β of TH was significantly higher in the group TH-40mg. In conclusion, TH injection maintains TA concentrations for a longer period of time than TA administration. Due to a possible saturation of esterases, the PK profiles associated to the high and low doses of TH were rather close suggesting that a dose of 10mg could provide an optimal benefit-risk.
