Pharmacokinetics of cephalothin: accumulation of its deacetylated metabolite in uremic patients.

The pharmacokinetics of cephalothin and its deacetyl metabolite were studied with use of a chemical assay involving high-pressure liquid chromatography. In seven patients with normal renal function, the half-life of cephalothin was about 28 min and concentrations of deacetylcephalothin in serum were low. In five patients with uremia, the half-life of cephalothin averaged 221 min and there was a continuous accumulation of the deacetyl metabolite in serum during treatment. Recovery of the drug in urine was quantitative when renal function was normal, whereas the amount of drug excreted was very low in cases of uremia. The results offer some explanation of the complex pharmacokinetics of cephalothin seen with microbiological tests and illustrate the usefulness of specific chemical assays, especially in the monitoring of serum concentrations of mixtures of antibiotic compounds that differ in antibacterial activity.