Mechanisms Responsible for Plasma Levels of Nafcillin Lower Than Those of Oxacillin

Abstract

Nafcillin sodium is known to give lower plasma levels than oxacillin sodium after both oral and parenteral administration. In the present study this difference was present in healthy volunteers within five minutes after a rapid intravenous infusion, and in uremic patients, plasma levels of nafcillin were only one half those of oxacillin after one hour. The factor mainly responsible was a much larger apparent volume of distribution for nafcillin, which seemed to result from a selective sequestration of the antibiotic in the liver and possibly in other tissues. With a continuous intravenous infusion, plasma levels of the two antibiotics were almost equal, in contrast to much higher levels of ampicillin than penicillin G, and of cephaloridine than cephalothin sodium, when studied similarly. These results were due to differences in renal and nonrenal clearances.