Pharmacokinetic prediction of nebulised polymyxin for pulmonary delivery

Abstract

Inhaled administration of polymyxin B is increasingly used to treat multi-drug resistant bacterial lung infections. However, the lack of clinical data on the pharmacokinetics of inhaled administration makes drug dose design, efficacy assessment and drug safety assessment a challenge. In this study, clinical data from intravenous injections were deconvoluted by an equal-step numerical deconvolution algorithm to derive the drug absorption rate of polymyxin B in vivo. The absorption rate was substituted into a published pulmonary absorption compartment model to predict the systemic pharmacokinetics of polymyxin B. It was demonstrated that the intravenous PK dataset with the pulmonary compartment model provided reliable estimates of the accuracy and bias of inhaled systemic pharmacokinetics.