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Epogen


Erythropoietin (EPO) Epoietin Alpha

Pharmaceutical Name: Epoietin Alpha
Drug Class: Erythropoiesis Stimulator
Active Life: Dependent on Injection Method Used


The primary growth factor in the regulation of the production of red blood cells in the human body is erythropoietin, commonly referred to as EPO (1). This hormone has been isolated and now produced in a synthetic form which is medically prescribed for the treatment of various forms of anemia by way of stimulating erythropoiesis, the creation of red blood cells in the body. By being able to manufacture a synthetic version of this hormone, the medical treatment of anemia has become far more effective in most patients and has eliminated the need for previously prescribed medications that were not nearly as efficient in treating the disease.

The synthetic version of erythropoietin, recombinant human erythropoietin (or epoetin alpha, r-HuEPO), is a purified single chain polypeptide hormone encompassing 165 amino acids in sequence (1). It is produced via a mechanism by which the human erythropoietin gene coding is introduced into animal cells. This mechanism creates a compound that is identical to that of the naturally produced hormone.

As for its use in athletics, epoietin alpha offers endurance athletes an effective means by which they are able to elevate their red blood cell production and concentration in a relatively convenient and efficient manner (2,3). Prior to the development of synthetic erythropoietin many endurance athletes relied on a procedure often referred to as ´┐Żblood doping´┐Ż. This simply referred to the action of removing and then storing a quantity of blood from an individual, and then transfusing that same blood back into the individual prior to an athletic event. This procedure results in a greater number of circulating red blood cells for the individual due to the fact that the body will reproduce the volume of blood initially removed, and then the blood that was removed along with the requisite red blood cells are added back. Epoietin alpha offers these same advantages without the need for the transfusion and storing of the blood of the individual. Obviously administering epoietin alpha is by far a more efficient and convenient method for achieving these results.

The reason that an increase in red blood cell count is so advantageous for endurance athletes is that red blood cells are responsible for delivering oxygen to muscle tissues. By having more of them available to fulfill this role, the blood of an athlete is far more efficient at delivering oxygen to muscles resulting in improvement in the endurance, strength and speed of an athlete (4). Therefore the use of epoietin alpha obviously helps an athlete in improving their various athletic responses, including oxygen uptake, exercise capacity and energy efficiency. For this reason, it should apparent why endurance athletes find this compound so beneficial.


Use/Dosing

Epoietin alpha can be administered using either intravenous or subcutaneous injections. The difference between the two methods is, not surprisingly, the rate at which the blood level of the compound peaks. When epoietin alpha is injected subcutaneously, blood levels of the compound will peak approximately twelve to eighteen hours after administration (3,4). Intravenous injections will peak rapidly after administration, due to the immediate entry of the drug into the blood stream. The half life of the drug is also greatly affected by the injection method used, with intravenous injections netting a half life of about four to five hours (1,5).

As for the dosing that is required to see results, medically the usual protocol is usually to prescribed roughly 15-60ius per kilogram of bodyweight three to four times per week for the patient (2,6). At these levels, an athlete looking for performance enhancement should see improvement. However, anecdotally many athletes have reported simply using 1000ius per day for the weeks running up to a competition, or something similar. However, there is innumerable different theories on exactly how much and how often doses should be administered.

As with most compounds the practice of starting out at lower dosages and then increasing them until a level that the athlete finds most beneficial is found, when balanced with the side effects that will result, should be used. The easiest and least problematic way of monitoring an individual's use of epoietin alpha would be to monitor his or her red blood cell count via blood tests. This way one is able to determine if and when their levels are reaching a level that they can become dangerous and a reduction in the amount of epoietin alpha being used needs to take place, or even the complete elimination of the use of the drug.

Once an individual begins using epoietin alpha and the peak levels of the compound are reached, the results of the drug should be experienced by the individual for several months after the administration of the drug is ceased (2,7). However the same is true of the side effects that may result. This again suggests that first time users need to increase their intake of the drug slowly so that if any side effects develop that they can be managed and do not develop rapidly. However of course, the benefits of epoietin alpha will slowly dissipate once the peak level of the compound begins to decline. This is why an athlete using the drug will want to have the blood concentration of the compound at or near it's maximum as close to the competition as possible.


Risks/Side Effects

Due to the very nature of the drug, numerous difficulties can arise in conjunction with the increased cell concentration in the blood of the user. In severe cases if cell concentrations reach high enough levels, this can result in the user suffering conditions such as stroke, heart attack and/or seizure in some cases (1,4). However, these conditions usually only result from a gross misapplication of dosing protocol and/or a prior medical condition.

A natural self-protection mechanism of the body is the production of antibodies in response to a foreign protein in the body. These antibodies will act against both the synthetic erythropoietin that is administered by the user, but also his or her naturally produced hormone. These antibodies will remain active for a time even once the administration of the synthetic erythropoietin is discontinued. This can result in the user suffering a sudden drop in their red blood cell count. For this reason, users should monitor their red blood cell count for a time after their use of the drug.

However, even when a user administers the appropriate dosages of the compound some moderate negative side effects are likely to occur. Due to the increase in cell concentration and volume in the blood, users are likely to experience an increase in blood pressure. Other commonly reported side effects include aching bones and joints, flu-like symptoms and chills (1). As well, whether using subcutaneous or intravenous injections to administer the drug, irritation at the injection site soon after it is completed is often experienced by users.

There are currently no ancillary drugs or supplements that can be used by an individual to help alleviate, or at the very least minimize, these side effects. If the user begins to find that the side effects become unbearable or that they jeopardize his or her health, the only action that can be taken is to cease administration of the compound. Once this is done, most symptoms should begin to dissipate within a few days time. However of course if these side effects become dangerous in their severity, medical assistance should be sought immediately.



References

1. Llewellyn, William, Anabolics 2004, 2003-4, Molecular Nutrition, p. 211

2. Shasha D, George MJ, Harrison LB. Once-weekly dosing of epoetin-alpha increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy. Cancer. 2003 Sep 1;98(5):1072-9

3. Ashenden MJ, Gore CJ, Parisotto R, Sharpe K, Hopkins WG, Hahn AG. Effect of altitude on second-generation blood tests to detect erythropoietin abuse by athletes. Haematologica. 2003; 88(9): 1053-62

4. Gaudard A, Varlet-Marie E, Bressolle F, Audran M. Drugs for increasing oxygen and their potential use in doping: a review. Sports Med. 2003; 33:187-212

5. Russell G, Gore CJ, Ashenden MJ, Parisotto R, Hahn AG. Effects of prolonged low doses of recombinant human erythropoietin during submaximal and maximal exercise. Eur J Appl Physiol 2002; 86:442-9

6. Schumacher YO, Schmid A, Lenz T, Keul J. Blood Testing in Sports - Haematological Profile of a Convicted Athlete. Clin J Sports Med 2001; 11:115-7

7. Nelson M, Ashenden M, Langshaw M, Popp H. Detection of homologous blood transfusion by flow cytometry: a deterrent against blood doping. Haematologica 2002; 87:881-2

8. Bressolle F, Audran M, Gareau R, Pham TN, Gomeni R. Comparison of a direct and indirect population pharmacodynamic model: application to recombinant human erythropoietin in athletes. J Pharmacokinet Biopharm 1997; 25:263-75






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