Intravenous colistimethate administration and colistin lung tissue concentrations

Pharmacokinetics of SPR206 in Plasma, Pulmonary Epithelial Lining Fluid, and Alveolar Macrophages following Intravenous Administration to Healthy Adult Subjects

“…Binding of colistin to mucin in airways results in subtherapeutic concentrations in the lung even with IV administration and could potentially promote development of resistance ( 47 , 48 ). While data are limited for polymyxin B and colistin, IV administration of colistin in critically ill patients resulted in undetectable levels in BAL fluid ( 49 ), which may have been the result of extensive tissue binding ( 50 ). Additionally, achieving an adequate dose of polymyxin B or colistin to reach a bactericidal concentration in the target tissue can pose a challenge because of the potential for nephrotoxicity ( 46 , 48 , 51 ).…”

Inhaled Antibiotics for Gram-Negative Respiratory Infections

“…Studies on the intrapulmonary concentrations of colistin after i.v. administration in humans have reported conflicting results (189)(190)(191), while the animal studies discussed above, in which CMS or colistin was given via inhalation, showed higher pulmonary concentrations with lower systemic concentrations. In a human study, the pulmonary PK of CMS in patients with VAT in an ICU were assessed after a single inhalation.…”

Pharmacokinetics of colistin after nebulization or intravenous administration of colistin methanesulphonate (Colimycin®) to cystic fibrosis patients

“…Colistin occupies an important place for the treatment of infections caused by multidrug resistant Gram negative bacteria, especially in cystic fibrosis (CF) patients persistently colonized by Pseudomonas aeruginosa. The pharmacokinetics (PK) of colistin, which is administrated as the prodrug colistin methanesulphonate (CMS), has been described in healthy volunteers [1], critically ill patients [2][3][4][5][6][7][8] and CF patients [9][10][11][12]. However these results are difficult to compare, due to a potential brand effect as shown in rats [13], to differences in samples processing and bioanalytical methods [14].…”