Pharmacokinetics of Polymyxins in Animals

Abstract

All of the small number of studies conducted during the second half of last century to investigate the pharmacokinetics of polymyxins in animals used microbiological methods to quantify the compounds in biological fluids. Those methods generally lacked the accuracy and precision required for such investigations and, in the case of studies involving administration of colistin methanesulfonate (CMS), ongoing conversion to colistin during microbiological incubation of collected samples artifactually elevated the measured concentration of colistin. The pharmacokinetic studies reviewed in this chapter involved use of more accurate, precise and specific methods for the measurement of the relevant compounds in biological matrices. The studies have been conducted in a number of pre-clinical animal species following administration via various routes (e.g. intravenous, intrapulmonary), and have provided important insights into not only the global pharmacokinetics as viewed from plasma but also the tissue distribution and handling by key organs particularly the kidneys.

Keywords: Animals; Colistimethate; Colistin; Global pharmacokinetics; Mechanisms involved in renal elimination; Polymyxin B; Tissue distribution.