recombinant erythropoietin, part four: administration

as with all drugs, the manner in which the drug is introduced into the body will greatly influence its physiological effects. performance enhancing drugs are the same in this respect, but the specifics of administration of peds plays a fundamentally more important role: evading detection. as ashenden et al. writes, "an athlete selecting a doping regimen would place greater emphasis on finding the highest dosage which evaded detection, rather than the lowest dosage which yielded a performance enhancement.” (ashenden et al., 2011). in this post we will continue the series on rhepo and consider the three closely related variables of administration: route, frequency and dosage. please note that the following does not constitute any medical or professional advice and is for education purposes only. the greater the public understanding of performance enhancing drugs, the better we will be able to address the greatest issue historically and currently affecting sport and health and fitness.

rhepo can be delivered in two primary ways, intravenously or subcutaneously. the most popular method in the 80s and 90s was to inject rhepo subcutaneously, that is underneath the skin. the benefit of doing this was primarily that it permitted a prolonged effect within the body due to a longer half life (halstenson et al., 1991). the site of injection is not so important, but any site where the injection could easily be placed between the skin and muscle is effective, and so the abdomen and thigh were/are commonly used.

the route of choice changed, thanks to efforts from notable doping experts like dr. ferrari and popularized in tyler hamilton’s book “the secret race” when it was discovered that intravenous injections could be used with smaller dosages. intravenous administration shortens the half-life of the drug, and given some studies have shown the period of detection could be as small as 12-18 hours following i.v. administration (ashenden et al., 2006) the risk of athletes being caught was greatly reduced.

the frequency of administration is of course based on the dosages used. it is common for athletes microdosing to administer rhepo every day (as hamilton discusses in his book), although this is rarely seen in the scientific literature. studies looking at microdosing athletes either for maintenance or to affect hematological changes will follow a schedule of dosing every 48-72 hours. for example, lundby et al. (2008) had a period of “boosting” in which athletes received injections every 48 hours, followed by a “maintenance” period of a single injection each week. the schedule of dosing is often left to an experienced pharmacologist, and will be influenced greatly by competition schedules. most courses of rhepo are going to be no longer than 4-6 weeks, and so cycling through variable dosages throughout a season is not uncommon.

in terms of the actual quantity of the drugs injected, once the above two variables are selected, the dosage is somewhat self-selected. in a study on the effectiveness of the biological passport to detect doping in athletes, ashenden and colleagues gradually increased the dosage from 10 IU/kg to 40 IU/kg with i.v. injections twice per week (2011). this was a more conservative approach than lundby et al., (2008) who used 5000 IUs every second day for 2 weeks followed by a single injection per week. even more aggressive still, ashenden et. al in 2006 used injections as high as 260 IU/kg, before reducing the dosage to only 10% of that value to maintain the large increase in hemoglobin. it is also common during rhepo use for athletes to use iron supplements (~100 mg injections) to facilitate hemoglobin synthesis.

clearly there are other aspects of rhepo administration that need to be considered by athletes and their doctors such as the pharmacological preparation (pascual et al., 2004), but this post hopefully serves as a basis for understanding the complexity of doping and the even more complex and difficult task of catching dopers.

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references

ashenden, m., varlet-marie, e., lasne, f., & audran, m. (2006). the effects of microdose recombinant human erythropoietin regimens in athletes. haematologica, 91(8), 1143-1144.

ashenden, m., gough, c. e., garnham, a., gore, c. j., & sharpe, k. (2011). current markers of the athlete blood passport do not flag microdose EPO doping. european journal of applied physiology, 111(9), 2307-2314.

halstenson, c. e., macres, m., katz, s. a., schnieders, j. r., watanabe, m., sobota, j. t., & abraham, p. a. (1991). comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. clinical pharmacology & therapeutics, 50(6), 702-712.

lundby, c., achman-andersen, n. j., thomsen, j. j., norgaard, a. m., & robach, p. (2008). testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing. journal of applied physiology, 105(2), 417-419.

pascual, j. a., belalcazar, v., de bolos, c., gutierrez, r., llop, e., & segura, j. (2004). recombinant erythropoietin and analogues: a challenge for doping control. therapeutic drug monitoring, 26(2), 175-179.