Biology Reference
In-Depth Information
weeks at a dose of 150 U/kg/week, then decreased the dose to 60 U/kg/week
for an additional five weeks. They determined that the VO
2 max
in week 12, four
weeks after the last dose, was still increased (3.1% to 4.5%). The hematocrit
remained increased for approximately 17 days after the last dose. Although
these results need to be confirmed,the data on low doses of rHuEPO suggest
that for a urine test for rHuEPO to be effective, it should be capable of detect-
ing rHuEPO for three to four weeks after discontinuing a dose of
60 U/kg/week. Such data are not available.
Another approach to the retrospectivity issue is to assume that the effect on
VO
2 max
lasts as long as the hematocrit or hemoglobin concentration remain
increased. While this assumption has not been directly investigated, it is rea-
sonable to assume that the duration of action on VO
2 max
will correlate with
hematocrit and hemoglobin concentration. In the three studies [40, 41, 74] that
measured hematocrits after rHuEPO was discontinued,a fixed dose of
rHuEPO (80-230 U/kg/week) was administered for three to five weeks.
During the rHuEPO administration phase, the hematocrit steadily increased
until a plateau of approximately 50% was reached at 12 to 14 days. The hema-
tocrit-time graphs of these studies show that the hematocrit is unchanged
(approximately 50%) for 12 to 20 days after rHuEPO is discontinued. The
hematocrit was last measured on days 24, 28, and 30 post-administration, and
for each study the hematocrit was still greater than that of the placebo group.
Thus performance as measured by VO
2 max
and the hematocrit appear to follow
more or less parallel time-courses, again consistent with three to four weeks of
enhancement after the last dose. An athlete could be enhanced and yet have a
negative urinary isoelectric focusing test.
Other erythropoietins
Athletes will experiment with other erythropoietic proteins as they become
available. If laboratories are to keep up with this fast-moving field, they need
detailed information on the new products, a reference standard for the product,
and at a minimum, a urine sample collected from a subject known to be receiv-
ing the substance. Ideally, the laboratories would administer the substance to
volunteers to obtain data on the isoform patterns and the pharmacokinetics of
detection. These requirements are not easy to fulfill, particularly in the United
States where ethics committees generally require that the drug be available as
Food and Drug Administration (FDA)-approved product. If not, the investiga-
tor must file an application for a Investigational New Drug, a lengthy, compli-
cated, and expensive process. Alternatively, the investigator may collaborate
with colleagues who are working under an FDA-approved protocol.
Epoetin alfa, epoetin beta, and darbepoetin alfa
The current isoelectric focusing test [67] is able to detect administration of
epoetin alfa, epoetin beta, and darbepoetin alfa [69, 70], allowing sport to con-
