The pharmacokinetics of reumycin, an antitumor antibiotic, was studied with high performance liquid chromatography in patients with tumors of the brain and kidneys. The drug was injected intravenously in single doses of 30-300 mg. It was shown that the pharmacokinetics of reumycin was nonlinear and within every dose could be depicted by a three- or two-compartmental model. Its nonlinearity was due to saturation of the antibiotic binding to blood plasma proteins. 20-40 per cent of the intact antibiotic was excreted with the urine unchanged, which indicated a significant role of extrarenal excretion of the antibiotic. The dose dependence of the pharmacokinetic parameters and in the particular of the area under the reumycin blood concentration on the time curve and cumulative renal excretion varied with patients. Distribution of patients by these parameters was bimodal. This factor and the differences in renal excretion caused significant variability in the reumycin pharmacokinetics, which required individualization and control of the antibiotic use in patients. The reumycin half-life in man predicted with the use of the Dedrick pharmacokinetic time scale by the data of experiments on rats appeared close to that established in patients (41 and 33.5 hours, respectively).
Antibiotics, Antineoplastic Brain Neoplasms