Polymyxin B: Pharmacokinetics of Single Doses Given Intravenously and Intramuscularly to Turkeys, and Minimal Inhibitory Concentrations for Escherichia coli and Pasteurella multocida.

The 50 % and 90 % minimal inhibitory concentrations (MIC50 and MIC90) of polymyxin B for avian Escherichia coli and Pasteurella multocida isolates were determined by the agar plate dilution method. Polymyxin B at approximate MIC level in serum was bactericidal for E. coli in 2 to 4 hours. Aqueous polymyxin B sulfate was administered by a single bolus intravenous injection into turkeys at 10,000 IU/kg, and by a single bolus intramuscular injection at 5,000, 10,000, or 20,000 IU/kg. Effective serum drug concentrations after intramuscular injection (MIC50 levels or greater) were maintained for E. coli for 7.0 hr (10,000 IU/kg) and 11.5 hr (20,000 IU/kg), and for P. multocida for 3.0 hr (10,000 IU/kg) and 4.1 hr (20,000 IU/kg). Pharmacokinetic parameters were calculated by non-compartmental methods. Elimination time half-lives, mean residence time, clearance, and apparent volume of distribution at steady state.(V_dss) were all much higher for i. m. injection of 20,000 IU/kg than for i.m. injection of 10,000 IU/kg. We postulate that there exists a minimal tissue-interaction threshold concentration (MTC) at which polymyxin B can enter previously unavailable compartments or bind to previously refractory tissue components. Bioavailability of polymyxin B injected i. m. was 0.904 for the 10,000 IU/kg dose and 0.675 for the 20,000 IU/kg dose. Dosage intervals necessary to produce minimal steady state concentrations (Css_min) equal to the MIC were calculated. Certain aspects of the use of the parameter V_dss, and limitations on the use of dosage interval calculations for polymyxin B, are discussed. One week after i.m. injection of polymyxin B at 10,000 IU/kg, high tissue drug levels were present, especially in bound form in liver. Following single injections, no toxic effects on turkeys were observed. [ABSTRACT FROM AUTHOR]