Pharmacokinetics of ingested Ursolic Acid supplements in healthy men

INTERVENTION: In a double‐blind, randomised, cross‐over design study to evaluate the bio‐availability Ursolic Acid in three different forms. Ursolic Acid will be ingested orally on 3 separate occasions with a minimum 7day wash‐out period in between doses. The study personnel will directly observe the participant ingesting the dose. The 3 single doses of ursolic acid will each contain 200mg ursolic acid within a capsule and will be indistinguishable from one‐another, but with the following differences: • UA‐Pow; capsule containing 200mg Ursolic acid in powder form • UA‐Phy; capsule containing 200mg Ursolic Acid within Phytosomes • UA‐Oil; capsule containing 200mg Ursolic Acid within Phytosomes suspended in oil CONDITION: muscle wasting; ; muscle wasting Musculoskeletal ‐ Other muscular and skeletal disorders PRIMARY OUTCOME: To determine if the composition of orally ingested UA impacts its bio‐availability in healthy men: This will be achieved through typical non‐compartmental pharmacokinetic analysis of ursolic acid in blood, such as:; • Maximum plasma concentration (C‐max) [ Time Frame: 6 hours] ; • Time at C‐max (T‐max); • Elimination half life (T‐1/2); • Elimination rate constant; • Area Under the Concentration Time‐Curve – The integral of the concentration‐time curve, from time zero to infinity (AUC 0–8) and from time zero to the last measurable time point (AUC0–t) ; • Volume of distribution; • Clearance rate; ; [Blood sampled at: 10, 20, 30, 45, 60, 75, 90, 120, 180, 240, 300 and 360 mins post consumption will be used to determine the availability of ursolic acid] SECONDARY OUTCOME: The secondary aim of this study is to determine the safety and tolerability of UA, this will be achieved by:[• The incidence of Treatment‐Emergent Adverse Events (Time frame: 24hrs) collected through continuous observations of AEs during a dosing visit, monitoring vital signs and spontaneous reporting of AEs. AE’s will be summarized by dose and severity. ; • The number of Serious Adverse Events ; • The number of Grade 3‐4 biochemical abnormalities (criteria defined by the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE) Version 4. ; ; Known adverse events: Possible hepatotoxicities. When 21 patients with advanced solid tumours were administered UA via IV infusion (doses of 56, 74, and 98mg/m2) 14% of patients experienced grade 2 GGT elevation. Two (10%) participants treated with 56 and 74mg/m2 UA had grade 1 abdominal distention. 1 (5%) had grade 2 ALT elevation. Grade 3 elevations in ALT at 130mg/m2. ; Hepatotoxicities will be assessed via blood sample ‐ using a liver function panel test. ; ; ] INCLUSION CRITERIA: • Healthy men aged between 18‐35 years • A BMI >18 and <27.99 kg/m2