If I'm correctly reading Miljenko's original comment (valuation thread #15165), 80-90% of the xyotax administered is recovered in the urine, intact. If the glutamate chains were not severed from the active ingredient, then logically that conjugated form could not have had a therapeutic effect in the patient.
That leaves the remaining 10-20% of the dose to do the heavy lifting.
So if the drug is excreted in its original formulation, differing rates of clearance and excretory pathways are not relevant variables since the excreted form could not have been biologically active. This relates to your point #2. Furthermore, for that 80-90% of drug, the rates of metabolism are not relevant since this fraction is excreted in an unmetabolized form. That relates to your point #3. And if such a large fraction is not metabolized at all, rates of transport into the tumour and other tissues is not a factor for this fraction of administered drug... relating to your point #1.
If we're to take Miljenko's assertions at face value, the fact that an inactive prodrug is largely excreted as an inactive prodrug simply suggests that this excreted fraction can not contribute to a therapeutic effect. In fact, this fully embraces the premise and theory behind conjugated drugs... :-)
In a large population of patients, I'm more inclined to believe that the fraction of excreted, conjugated drug is unlikely to be as high as 80-90%. If it was so, the median survival of stellar 3 would not have been lengthened compared to historical controls. |
