Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product

• Published in: BMC pharmacology & toxicology Vol. 21; no. 1; pp. 88 - 12
• Main Authors: Cameron, Beth R., Ferreira, Ludvina, MacDonald, I. David
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.12.2020; BioMed Central; BMC
• Subjects: Absorption; Ademetionine; Adenosylmethionine; Adomet; Bioavailability; Calendars; Comparative analysis; Dietary supplements; Drug dosages; Electrocardiography; Food; Formulation; Hepatitis; High-performance liquid chromatography; Liquid chromatography; Medical laboratories; Model testing; Pharmacokinetics; Pharmacology; Plasma; Relative bioavailability; S-Adenosylmethionine; Safety; Statistical analysis; Statistical methods; Variance analysis; Vital signs; United States > US; Adomet; Ademetionine; Relative bioavailability; Pharmacokinetics; S-adenosylmethionine; Formulation
• ISSN: 2050-6511; 2050-6511
• DOI: 10.1186/s40360-020-00466-7

A novel, high bioavailability oral, enteric coated tablet formulation of S-adenosylmethionine (MSI-195) has been developed for life science application. The present research reports on a Phase 1 study to (i) determine the safety of single doses of MSI-195 (ii) to determine the dose proportionality of MSI-195 at doses of 400, 800 and 1600 mg (iii) determine the pharmacokinetics of MSI-195 compared with a commercial reference product (SAM-e Complete™) over 24 h and (iv) to determine the effect of food on the pharmacokinetic profile of MSI-195 in human subjects. This study was a pharmacokinetic and safety evaluation of MSI-195 and a commercial comparator broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195. Plasma samples were collected and assayed for S-adenosylmethionine using a validated HPLC method with MS/MS detection. The main absorption and disposition parameters were calculated using a non-compartmental approach with a log-linear terminal phase assumption. Statistical analysis was based on an ANOVA model or t test as appropriate. MSI-195 was found to be generally well tolerated with an adverse event profile similar to the SAM-e Complete™ comparator product. The relative bioavailability of MSI-195 was approximately 2.8-fold higher than SAM-e Complete based on area under the curve (AUC) ratios for the two products and the MSI-195 formulation exposure based on AUC was found to be approximately dose proportional. There was a significant food effect for MSI-195 with a delayed time to maximum absorption T , going from 4.5 h under fasted conditions to 13 h under fed conditions, and area under the curve with food reduced to 55% of that seen under fasting conditions. The overall conclusion was that MSI-195 was well tolerated and has markedly higher bioavailability compared with both the SAM-e Complete™ commercial product tested and, on a per mg basis, products reported in other literature. ClinicalTrials.gov, identifier NCT04623034 . Retrospectively registered Nov 9, 2020.