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The penetration of five cephalosporins into interstitial fluid was investigated by a new method employing cotton threads implanted subcutaneously. Penetration after short bolus injections, calculated as area under interstitial fluid level curve divided by area under serum level curve x 100, was 47.0% for cephradine, 30.6% for cefuroxime, 26.7% for cefotaxime, 24.6% for cefoxitin, and 9.6% for cefoperazone. There was an inverse correlation between the degree of penetration and serum protein binding with r = -0.97. The area under interstitial fluid level curves was the same whether the drugs were administered as short bolus injections or short time infusions.

Influence of serum protein binding and mode of administration on penetration of five cephalosporins into subcutaneous tissue fluid in humans