Gastrointestinal Tolerability and Absorption of R‐ Versus R,S‐Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial

• Published in: Journal of clinical pharmacology 2020-08, Vol.60 (8), p.1099-1106
• Main Authors: Cameron, Michelle, Taylor, Cassidy, Lapidus, Jodi, Ramsey, Katrina, Koop, Dennis, Spain, Rebecca
• Format: Article
• Language: English
• Subjects: absorption; Lipoic acid; Multiple sclerosis; pharmacokinetics; racemic; Side effects; thioctic acid; tolerability
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/jcph.1605

We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption of R‐lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single‐center, double‐blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600 mg of R‐LA or 1200 mg of a 1:1 racemic R,S‐LA mixture in single daily doses for 7 to 10 days, underwent a washout of at least 7 days, and then took the other form of LA for 7 to 10 days. At the end of each period on LA, GI symptoms were assessed with GI questions from the Monitoring of Side Effects Scale. Serum LA concentrations were measured before and 60, 90, 120, 180, and 240 minutes after the first and last day's dose of each form of LA to derive an area under the plasma concentration–time curve (AUC) and maximum serum concentration (Cmax). Twenty participants enrolled (12 women; 15 secondary progressive MS, 5 primary progressive MS; mean age, 59.6 years). Two withdrew early due to symptoms while taking R,S‐LA, and one withdrew early while taking R‐LA. The mean GI Monitoring of Side Effects Scale score was 1.7 points lower on R‐LA than on R,S‐LA (P = .069), and there were fewer reports of each GI side effect when taking the R‐LA than the R,S‐LA (31 vs 60; P = .025). The AUC and Cmax for R‐LA were bioequivalent for the 2 formulations (90% confidence intervals 97.4% to 99.3% for AUC and 93.4% to 98.2% for Cmax). This study supports that in people with progressive MS, there is better GI tolerability and bioequivalent serum absorption of R‐LA when 600 mg of R‐LA is taken as R‐LA alone than when taken in a 1:1 racemic R,S‐LA mixture.