TY - JOUR
T1 - Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis
T2 - A Randomized Crossover Trial
AU - Cameron, Michelle
AU - Taylor, Cassidy
AU - Lapidus, Jodi
AU - Ramsey, Katrina
AU - Koop, Dennis
AU - Spain, Rebecca
N1 - Publisher Copyright:
© 2020, The American College of Clinical Pharmacology
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - absorption
KW - lipoic acid
KW - multiple sclerosis
KW - pharmacokinetics
KW - racemic
KW - thioctic acid
KW - tolerability
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U2 - 10.1002/jcph.1605
DO - 10.1002/jcph.1605
M3 - Article
C2 - 32212340
AN - SCOPUS:85082736339
SN - 0091-2700
VL - 60
SP - 1099
EP - 1106
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 8
ER -