Determination of detection windows of Mildronate (Meldonium) in urine after single and multiple oral administraation in healthy volunteers

Code: R16R01WS 

In this research project urinary excretion profiles and corresponding urinary detection windows of Mildronate (Meldonium) after single and multiple oral applications of the drug should be investigated in healthy volunteers. The results of the study will have an immediate impact on current Adverse Analytical Findings of Mildronate. The obtained pharmacokinetic data will help to interpret the estimated urinary concentrations and may be helpful in cases, where athletes claim that they have taken high doses of Mildronate before the compound was implemented in the 2016 WADA prohibited list.

Within the research project the following activities are planned: 1. Application for ethical approval

2. Administration studies after single- and multiple oral applications of Mildronate

(dosages and interval of drug ingestion based on recent publications and clinical recommendations [8,9]).

o single-dose phase: volunteers receive one dose of 1500 mg Mildronate and collect all urine samples for four to five consecutive days.

o multiple-dose phase: volunteers receive 500 mg Mildronate three times a day for six days. During this administration period the volunteers should collect all urine samples. After the application period (from day 7 on) the volunteers should collect one urine sample per day until the urine is blank.

o The volunteers should provide information about their anthropometric data (age, height, weight) and the date and time urine samples were collected.

3. Analyzing of urine samples using LC-MS/MS and HILIC/HRMS/MS approaches. [4]

4. Investigation of urinary excretion profiles of Mildronate and a comparison of the urinary detection windows after single and multiple oral applications of the drug.

5. Publication of the data in an international journal

Main Findings: 

Preliminary results: So far, only one excretion study is published, which shows the urinary detection window for the application of a single dose of 250 mg Mildronate. In this study Mildronate was detectable up to 50 hours after intake. [7] However, the pharmacological dosage recommendation for Mildronate is several times higher.

Furthermore, two studies demonstrate pharmacokinetic profiles of Mildronate: 1.) after intravenously administration and 2.) after oral application in human plasma. These findings suggest, that multiple administration leads to accumulation of Mildronate in human plasma. [8,9] No data are available concerning the excretion profile after single and high doses of oral administered Mildronate in urine.