DISAPPEARANCE KINETICS OF SOLUTES FROM SYNOVIAL-FLUID AFTER INTRAARTICULAR INJECTION

1 Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [I-125]-albumin was injected into a given joint to yield target concentrations of approximately 20 mu g ml(-1) f or diclofenac, salicylate and paracetamol and 10(8) counts ml(-1) for [I-125]-albumin. 2 Paracetamol, salicylate and diclofenac were analyse d in synovial fluid by h.p.l.c. [I-125]-albumin was analysed using gam ma counting. 3 The clearances (+/- s.d.) obtained for the solutes were [I-125]-albumin (0.0053 +/- 0.0019 1 h(-1)), diclofenac (0.0096 +/- 0 .0061 1 h(-1)), salicylate (0.024 +/- 0.022 1 h(-1)) and paracetamol ( 0.055 +/- 0.041 1 h(-1)). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, less than or equal to 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4 Diffusion of unbound solut e through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclo fenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of so lute bound to albumin. 5 An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was deve loped to include both diffusion of unbound solute and albumin flux. Mo st solutes appear to satisfy the conditions in which this expression r educes to the limiting case where the unbound concentration of the sol ute is identical in the synovial fluid and plasma under steady state c onditions.