Fate of oral³⁵S-cloxacillin in man

Summary

³⁵S-Cloxacillin was administered orally, intravenously or by intrajejunal instillation to healthy subjects. An oral dose of the³⁵S-penicilloic acid of cloxacillin was given to two subjects. The absorption of radioactive material from the upper part of the digestive tract was calculated by reference to an unabsorbed marker in the test solution. After an oral dose of³⁵S-cloxacillin, the average cumulative absorption of radioactivity from the upper jejunum was 60%, and although some³⁵S-cloxacillin was degraded in the stomach, the uptake of radioactivity appeared mainly to represent absorption of intact drug. The uptake of radioactivity after administration of³⁵S-penicilloic acid was about 30% of that of labelled cloxacillin. After³⁵S-cloxacillin, up to 25% of radioactivity in urine and about 80% of that in bile were attached to microbiologically inactive cloxacillin metabolite(s). The almost identical pattern of degradation after oral and intravenous administration of³⁵S-cloxacillin suggested that the metabolite(s) were formed outside the gastrointestinal tract. A comparison of the concentration of total cloxacillin equivalents (measured as total radioactivity) and intact cloxacillin (determined by microbiological assay) showed that a substantial part of the plasma radioactivity represented microbiologically inactive metabolites of cloxacillin. The half-life of the plasma label was much longer than that reported for the microbiologically active compound.