Effects of extracorporeal membrane oxygenation on the pharmacokinetics and tissue penetration rates of vancomycin and linezolid: data from Landrace pigs.

OBJECTIVES This study investigated whether extracorporeal membrane oxygenation (ECMO) alters the pharmacokinetics or tissue penetration of vancomycin and linezolid, assessed the need for dose adjustments during ECMO support and evaluated the suitability of each drug for different infection sites.

METHODS Each Landrace pig underwent two sequential experiments, one without ECMO and one with ECMO, separated by more than 4 weeks. Blood samples were collected before and after intravenous infusion of vancomycin and linezolid and tissue samples were obtained immediately after the ECMO period. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using a non-compartmental model and tissue penetration rates were determined by comparing tissue concentrations with serum levels before euthanasia.

RESULTS ECMO did not significantly influence the pharmacokinetics of vancomycin or linezolid. Vancomycin penetration was highest in the kidney (390%) and alveolar epithelial lining fluid (120%), with lower levels in the lung, liver, spleen and skin (10%-20%) and minimal penetration in the small intestine and muscle (<10%). Linezolid demonstrated stronger tissue penetration, reaching 236% in alveolar epithelial lining fluid and 20%-30% in the kidney and liver.

CONCLUSIONS ECMO does not affect the pharmacokinetics of vancomycin or linezolid, suggesting that dose adjustments are unnecessary. Both drugs demonstrate wide tissue distribution during ECMO and are suitable treatment options in this setting.