Pharmacokinetics and Utilization of Alpha Lipoic Acid; a Proposed Therapeutic Aid for California Sea Lions (Zalophus californianus) with Domoic Acid Toxicosis
Domoic acid (DA) is a potent neurotoxin which, when ingested, can cause neurological dysfunction and cardiotoxicity by binding glutamate receptors. Glutamate receptor over-excitation results in continuous cellular activation, secondary oxidative damage, and cell death. Toxicosis causes disorientation and seizures, and anti-seizure medications are the primary treatment. Alpha lipoic acid (ALA), a glutathione precursor, can cross the blood-brain barrier to provide local antioxidant availability. Hundreds of stranded California sea lions (CSL: Zalophus californianus) are diagnosed annually with DA toxicosis, thus are an appropriate animal in which to establish ALA dosing recommendations. The objective of this study was to determine the population pharmacokinetics of a single subcutaneous dose of ALA at 10 and 20 mg/kg, administered to healthy CSL following rehabilitation at The Marine Mammal Center. Blood was collected at two time points between 15 minutes and 24 hours post-administration from CSL given one of these doses. Serum ALA concentrations were measured by liquid chromatography-mass spectrometry. Cmax was 1580 and 4173 ng/ml and Tmax was 45 and 30 minutes for dosages of 10 and 20 mg/kg respectively. Serum from 12 sea lions with DA toxicosis treated with 10 mg/kg ALA between 3–13 days had measurable levels, and ALA was measured in cerebrospinal fluid from 2 treated CSL. ALA levels in humans may be therapeutic at 4–5 ug/ml or higher,1 thus in California sea lions, 20 mg/kg administered subcutaneously may be sufficient to achieve a therapeutic level in this species, however dosing interval and determination of efficacy require additional investigation.
This study was made possible by a grant from the AAZV Zoological Medicine and Wild Animal Health Fund. The authors thank Carlos Rios and the dedicated animal care staff and volunteers at The Marine Mammal Center for their excellent animal care, and Golden Gate Pharmacy and Animal Necessity® for their assistance with this project.
1. Maczurek A, Hager K, Kenklies M, Sharman M, Martins R, Engel J, Carlson DA, Munch G. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease. Advanced Drug Delivery Reviews. 2008;60:1463–1470.