Pharmacokinetics of Polymyxins in Animals

Area of Science:

• Veterinary Pharmacology
• Pharmacokinetics
• Antimicrobial Agents

Background:

• Previous polymyxin pharmacokinetic studies in animals relied on less accurate microbiological assays.
• Microbiological methods often yielded artifactually high colistin concentrations due to sample degradation.

Purpose of the Study:

• To review and synthesize findings from recent, more accurate pharmacokinetic studies of polymyxins in pre-clinical animal models.
• To provide a comprehensive understanding of polymyxin pharmacokinetics, including tissue distribution and organ handling.

Main Methods:

• Utilized accurate, precise, and specific bioanalytical methods for quantifying polymyxins in biological matrices.
• Reviewed studies involving various administration routes (e.g., intravenous, intrapulmonary) in diverse pre-clinical species.

Main Results:

• Established more reliable pharmacokinetic profiles for polymyxins in animals.
• Detailed insights into polymyxin tissue distribution and elimination, particularly renal handling.
• Identified limitations of older microbiological assay methods.

Conclusions:

• Modern analytical techniques provide superior accuracy for polymyxin pharmacokinetic studies in animals.
• Enhanced understanding of polymyxin disposition in key organs like the kidneys is crucial for drug development and use.