Effect of protein binding on levels of ampicillin and cloxacillin in synovial fluid

The penetration of ampicillin and cloxacillin into synOVial fluid has been measured after oral administration of these penicillins to patients with osteoarthritis or rheumatoid arthritis. The results show that both penicillins diffuse readily into synovial i0int fluid and that concentrations inhibitory for bacteria commonly associated with septic arthritis can be readily attained in infected synOVial ioints following systemic administration of ampicillin or cloxacillin. The penicillins differed with respect to the levels appearing in the synovial fluid relative to the levels in serum; in the case of ampicillin (which is not highly bound to serum) the total levels in synovial fluid were similar to the total serum levels, whereas with cloxacillin (which is highly bound to serum) the total levels in synOVial fluid were notably lower than in serum. However, the unbound levels of cloxacillin in synOVial fluid and serum were similar, as with ampicillin, indicating that the degree of binding is imp01tant in distribution between serum and tissue.