Sustained-release dexamethasone palmitate - Pharmacokinetics and efficacy in patients with activated inflammatory osteoarthritis of the knee

Objective: To assess the pharmacokinetics. clinical efficacy and tolerabili ty of a single intra-articular injection of dexamethasone palmitate (Lipota lon((R)); Merckle GmbH) 4 or 12mg over a period of 4 weeks. Design: Randomised. parallel-group, phase II study. Patients and Participants: 24 male and female patients aged 63.3 +/- 5.5 ye ars (range 56 to 75 years) with activated inflammatory osteoarthritis of th e knee. Methods: Serum concentrations of free dexamethasone, arising from esterase breakdown of dexamethasone palmitate, were measured by radioimmunassay. The linearity of both doses was calculated by Wilcoxon's method. The profile o f absorption was evaluated by the Wagner Nelson method. Clinical efficacy w as assessed by an index of activity, and pain, efficacy and tolerability we re evaluated by descriptive methods. Results: The mean peak serum concentrations of dexamethasone were attained after 14 hours (4mg) and 21 hours(12mg), and were 6.36 and 10.97 mug/L, res pectively. 90% of the dose was absorbed within 24 and 48 hours, respectivel y. 10% was not absorbed until day 28. Endogenous cortisol levels fell trans iently to approximately 10% of baseline levels after 24 to 36 hours, but re turned to normal within 3 to 5 days. Pain reduction and clinical improvemen t were maintained over the complete observation period of 4 weeks. No adver se events were observed. Conclusion: Dexamethasone palmitate exhibits short- to medium-term sustaine d-release properties, together with good efficacy and very good tolerabilit y.