Kidney function as a key driver of the pharmacokinetic response to high‐dose L‐carnitine in septic shock

摘要: Study Objective Levocarnitine (L‐carnitine) has shown promise as a metabolic‐therapeutic for septic shock, where mortality approaches 40%. However, high‐dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations. We sought to describe the population pharmacokinetics (PK) of high‐dose L‐carnitine, test various estimates of kidney function, and assess the correlation of PK parameters with pre‐treatment metabolites in describing drug response for patients with septic shock. Design Population PK analysis was done with baseline normalized concentrations using nonlinear mixed effect models in the modeling platform Monolix. Various estimates of kidney function, patient demographics, dose received, and organ dysfunction were tested as population covariates. Data Source We leveraged serum samples and metabolomics data from a phase II trial of L‐carnitine in …