Mechanisms Responsible for the Blood Level Differences of Isoxazolyl Penicillins

Abstract

With continuous intravenous infusions plasma levels of dicloxacillin sodium monohydrate were much higher, and the calculated plasma half-life was much longer, than for cloxacillin monohydrate sodium and oxacillin sodium. Renal clearance values for oxacillin (226.8 ml/min) were twice those for dicloxacillin, with intermediate values for cloxacillin. In uremic patients the plasma half-life of oxacillin was only slightly longer (31 vs 23 minutes) than in healthy subjects, but the differences were considerably greater for cloxacillin (48 vs 25 minutes) and dicloxacillin (62 vs 42 minutes). Thus, the addition of one (cloxacillin) or two (dicloxacillin) chlorine atoms on the oxacillin molecule causes a progressive decrease in renal clearance and increase in resistance to degradation by the liver, and these characteristics are important in determining the differences in blood levels. Dicloxacillin appears to have significant pharmacological advantages over cloxacillin and oxacillin.