1. Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm.
- Author
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Tremoulet AH, Jain S, Jone PN, Best BM, Duxbury EH, Franco A, Printz B, Dominguez SR, Heizer H, Anderson MS, Glodé MP, He F, Padilla RL, Shimizu C, Bainto E, Pancheri J, Cohen HJ, Whitin JC, and Burns JC
- Subjects
- Administration, Oral, Adolescent, Atorvastatin adverse effects, Atorvastatin pharmacokinetics, Child, Child, Preschool, Coronary Aneurysm etiology, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacokinetics, Male, Mucocutaneous Lymph Node Syndrome complications, Atorvastatin administration & dosage, Coronary Aneurysm drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Mucocutaneous Lymph Node Syndrome drug therapy
- Abstract
Objectives: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA)., Study Design: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment., Results: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls., Conclusions: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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