Pharmacokinetics Could Save Maria Sharapova
MAY 15, 2016 @ 10:23 AM
Bruce Y. Lee , CONTRIBUTOR
While former tennis star Chris Evert has said that tennis player Maria Sharapova has no friends on the tennis tour, having “isolated herself,” from other players, pharmacokinetics could end up being Sharapova’s best friend. Who or what exactly is pharmacokinetics? (No, it’s not some type of alternative rock group.)
Well, as you may know, the World Anti-Doping Agency (WADA) found a sample that Sharapova provided on January 26, 2016, at the Australian Open to be positive for meldonium. On January 1, 2016, meldonium became a banned substance, deemed a performance enhancing drug (PED). The rationale is that meldonium (sold under the brand name midronate) can increase endurance and exercise tolerance and speed recovery by improving blood flow and acting on the central nervous system. The positive test then led to Sharapova, one of the world’s highest earning athletes, being provisionally banned from the professional tennis tour. The length of the ban remains to be determined. This ABC News report shows what happened:
On May 18, a one or two day hearing will commence in London, allowing Sharapova to plead for a lesser punishment. So what may Sharapova’s main argument be and what could get Sharapova off the hook? Pharmacokinetics.
An American Society of Health System Pharmacists publication defines pharmacokinetics as “the study of the time course of drug absorption, distribution, metabolism, and excretion.” In other words, pharmokinetics encompasses where drugs go in the body, how long they stay in different parts of the body, how are the drugs broken down, where the drugs end up, and how do they leave the body. All medications and other substances enter the body somehow, through the mouth, the skin, the nose, and other body openings that you can imagine. As the substance moves through different parts of the body, whether its the stomach, muscle, fat, or blood, different enzymes and conditions (e.g., acid in the stomach) may break down or alter the substance. When the substance also may change when it takes the action it was designed to do. All along the body may excrete the substance through urine, stool, sweat, bile, or other exits from the body.
The field of pharmacokinetics is very important in drug design, development, and testing but doesn’t always get the attention that it deserves. A drug cannot work if it does not get to where it is supposed to go and stay there long enough. Similarly, overdoses and bad side effects of a drug may occur if the drug remains active and hangs around certain parts of the body too long. Pharmacokinetics is what determines the dose of a medication and the frequency you have to take the medication. For instance, drugs that tend to remain active in the body for long periods of time, you may want to use a lower dose and take the drug less frequently. If you want to run a pharmaceutical company (or an anti-doping agency, or a doping operation…which you really shouldn’t be doing), make sure you have experts in pharmacokinetics. Here is some more information on pharmacokinectics.
While the half-life of meldonium appears to be four to six hours, Grindeks, the Latvian manufacturer of the drug, is claiming that meldonium may linger in the body for months. (By the way, Grindeks would be a great Lord of the Rings character name.) The half-life of a drug is the time it takes for half of the dose of a drug to no longer have an effect of the body, because the drug is broken down into inactive parts or has left the part of the body where it has an effect. Therefore, if the half-life of a drug is 4 hours, and you take 500 mg of the drug at noon, by 4 pm, only 250 mg will still be active in your body.
The argument that Sharapova’s team may present is that the drug remained in her system from taking it before the ban of meldonium went into effect. If she had taken her last dose December 31, 2015, then the drug test would have occurred 26 to 27 days later. Whether meldonium could have been detected in her testing sample that late depends both on the pharmacokinetics of meldonium and the sensitivity of the test (i.e., how well the test picks up a particular substance when the substance is present).
Reported half-lives tend to be averages or medians, as many factors can affect how quickly a drug is broken down and how long it remains in your body. Your weight, your metabolism, your health, what you eat and drink, your age, your physical activity, and even the time of day and year are just some of the things that can affect the half-life of a medication. However, while half-lives may vary from person to person by hours, they tend not to vary by weeks or months, unless a person has a accompanying serious medical condition such as kidney or liver disease that impair the person’s ability to excrete the drug. Sharapova, presumably, is healthy enough to be a world class athlete. Also, just because a drug is still in the body, does not mean the drug will be in the sample and the test is sensitive enough to detect it. For example, if a drug is hanging out in a person’s blood, a urine sample may not have high enough levels to be detectable. Therefore, the key will be determining how long can meldonium remain detectable in a healthy person’s testing sample…and whether the test checks for the actual levels of the drug or just for the presence of the drug.
It’s highly likely that some currently acceptable medications and other substances will eventually make it to the list of banned PEDs. WADA cannot possibly anticipate every new concoction that will come down the pike. Moreover, the line between what is and isn’t a PED can be very fuzzy. Former National Basketball Association (NBA) player and current Golden State Warriors coach Steve Kerr once described the anti-inflammatory medication Vioxx as a PED, saying that near the end of his career it allowed him to play by relieving the pain in his joints. Thus, the banned substance list usually lags what is currently being used.
Therefore, the Sharapova case may help determine how WADA and other regulatory bodies handle testing for substances when they first move on to the banned list. Should there be a grace period after a substance has been banned based on the substance’s pharmacokinetics? In other words, once a substance is officially banned, perhaps athletes can test positive without facing penalties for a length of time determined by studies that show how long a drug can stay in the body? Did WADA anticipate that a case like this may happen and thoroughly study the pharmacokinetics of meldonium before declaring it a PED? When an athletes sees that a formerly allowed substance is newly banned, should they inform WADA about possible pharmacokinetic issues that may lead to a positive test? Unless pharmacokinetics help shape anti-doping testing and policies, more and more such disputes may occur in the future.
Thus, Sharapova may have an opening for a comeback, which could potentially occur at Wimbledon. Regardless of the outcome of the appeal, athletes, WADA, and other sports officials may pay more attention to pharmacokinetics in the future.
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Но можете быть убеждены адвокаты Марии поставять этот вопрос.
Если Трибунал накажет Марию строже, чем адвокаты думают, тогда Мария пойдет в суд.
Вряд ли кому интересно будет писать или читать про Юлю Ефимову или Кулижникова, они хоть и звезды в своем виде спорта, но с Машей им никак сравниться. Машу знают все.