Determination of pharmacokinetic properties of prohibited substances to optimize a process of doping test

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17840
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Hiroshima International University
• Principal Investigator: Oda Keisuke 広島国際大学, 薬学部, 講師 (60712594)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ドーピング / 薬物動態 / 腎排泄 / LC-MS/MS

Outline of Final Research Achievements

The fate of 1, 3-dimethylamylamine (DMAA), a prohibited substance to athletes, was evaluated by determining plasma concentrations, urinary excretion rate, and tissue distribution after intravenous, oral and transdermal administration in rats. DMAA administered intravenously disappeared from plasma according to a biexponential curve. During 6 h after intravenous administration, 35.2% of DMAA dose was excreted into urine as an intact form. Alkalized urine pH resulted in decreased urinary excretion rate and higher plasma concentrations of DMAA.The mean oral bioavailability of DMAA was 43.6%. When DMAA was applied to the skin, DMAA was recovered by 5.4% of dose in the urine for 7 days. In conclusion, DMAA was thought to be absorbed from anywhere, including the skin and distributed to various tissues. Long-term retention of DMAA in the body was, at least partly, due to the repeated reabsorption in renal tubules, though the extent of DMAA reabsorption depends on urine pH.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

今回得られた知見は、ドーピング禁止物質の生体内運命を明らかにし、その制御因子を同定するものである。尿のpHが変化することにより、ドーピング禁止物質の尿中排泄が変化するため、検査時の「陽性・陰性」判断を誤ってしまう可能性が考えられる。また、DMAAのような塩基性の脂溶性低分子化合物の場合、皮膚などからも吸収されてしまうため、経口摂取以外の体内侵入経路を考慮する必要がある。このように、ドーピング禁止物質の体内動態変動要因を社会に広く周知させることにより、「うっかりドーピング」の回避、ドーピング検査の最適化に寄与できるものと考えられる。