Atorvastatin Safety And Pharmacokinetics In Acute Kawasaki Disease Patients With Coronary Artery Abnormalities

Introduction: Despite therapy with intravenous immunoglobulin, 25% of children with Kawasaki disease (KD) develop coronary artery abnormalities (CAA) and endothelial cell (EC) dysfunction. Based on the pleiotropic effects of statins on restoring EC homeostasis, we performed a Phase I clinical trial of atorvastatin for acute KD patients with early CAA. Hypothesis: A six-week (wk) course of atorvastatin in acute KD patients (pts) with CAA will be safe, well- tolerated and restore EC homeostasis. Methods: This two-center, Phase I, open label, dose escalation trial enrolled acute KD subjects aged 2-17 years with an initial CA Z score ≥ 2.5 in a 6-wk study of atorvastatin (0.125, 0.25, 0.5 and 0.75 mg/kg/day). Demographic, clinical and laboratory data, and echo core lab readings were collected at baseline, 2 and 6 wks. Plasma atorvastatin and o-hydroxyatorvastatin levels were assessed by mass spectrometry and pharmacokinetic parameters were calculated. Brain 24-hydroxycholesterol levels were assessed in plasma...