Metabolic disposition of cephalothin and deacetylcephalothin in children and adults: Comparison of high‐performance liquid chromatographic and microbial assay procedures

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Abstract
A highly specific method utilizing ion‐pair extraction and high‐pressure liquid chromatography has been developed for the analysis of cephalothin and deacetylcephalothin in biological specimens. Kinetic data obtained in children and adults were used to compare this method of analysis with microbial assay procedures. In this study serum elimination curves were developed following the intravenous administration of cephalothin to adults (5 to 37.5 mg/kg) and children (10 to 25 mg/kg). The elimination half‐life (t½ of cephalothin from serum was 13.5 ± 3.2 min in adults and 18.6 ± 4.6 min in children (p < 0.05). The mean KEL in adults was 3.15 ± 0.2 hr‐1 and 2.35 ± 0.51 hr‐1 in children; the specific VD in adults was 0.21 ± 0.03 Llkg as compared to 0.93 ± 0.15 Llkg in children. The primary metabolite of cephalothin, deacetylcephalothin, was present in sera and urine obtained from adult subjects. Approximately 25% of the cephalothin dose administered was eliminated in urine as deacetylcephalothin. Significant differences were observed between microbial and high‐pressure liquid chromatographic assay procedures in that the former estimated higher concentrations of cephalothin in urine specimens, probably due to the presence of high concentrations of deacetylcephalothin or other active metabolites. The rapid plasma clearance of cephalothin suggests that clinical regimens using 4‐to 6‐hr dosage intervals may result in drug levels which are below the minimum inhibitory concentration of most susceptible organisms for approximately 50% of each treatment period.

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