I have accidentally made a discovery while slowly increasing day-by-day the amount of fat/oil boost given to one Zytiga pill. Four each day are FDA approved and known to have more than 94% just go thru you and into the toilet, if taken on a two hour empty stomach as Janssen, the maker studied in its clinical trials. Not very desirable when bottle of 120 pills cost about 1000 dollars! Also known* was that if taken with a "High Fat Meal" (57% fat and 825 calories) the absorption would increase 17 fold. Note 6x17 = 102% absorption is impossible, so implies less 6% enters the blood if taken as FDA has approved. That recommendation was made because an over doses can seriously damage the liver and the amount of fat in food is very variable.
An empty stomach seemed to be the only way to assure reproducibility, but I carefully measure with medical syringe the volume of soy oil and grams of butter I take 1 Z-pill with. My boosts, with monthly checks of blood chemistry, especially liver damage indicators ALT & AST finally became 5dl + 25 grams with blood pressure measure every 15 minutes after swallowing the pill with this boost in a 50/50 water emulsion.
First and second days using this boost had everything OK, but third day I became quite sick about 10 minutes after swallowing the pill with this boost. My systolic BP measurement was 160mmHg. Even only 140 is high for me and normal it is usually less than 135x85. The illness was sort of like nausea + dizziness but I had no urge to vomit. I named this new type of illness: MDU, Mental Disturbance Unease.
Next day after MDU, I used only 1dl of oil but kept the 25 grams of butter. (I buy it in 200g brick shaped blocks; cut it carefully into 8 equal pieces; 200/8 =25 g). This next day, my PB was normal with no hint of MDU, so the next day I used 2dl and it strangely had a peak BPs slightly less than the prior day with only 1dl and still no hint of MDU, so the next day I used 3dl of soy oil with 25g of butter (and still do).
The most plausible reason why (and my "accidental discovery") that 2dl had lower peak BPs than day with only 1dl of oil boost was that the three days of 5dl over dose with drug accumulation inside the cells had ended two days earlier, not just one. I. e. the "half-life" inside the cells must be about 3 days, not the 15 minutes it is, according to the literature, in the blood with the liver actively removing it. This may already be known, but I have very extensively read the literature and never saw any report on the "inside the cells half life." That "accumulation hypothesis” also explains why I had no ill effect, or even significant elevation of BP when I had used 5dl of oil +25 grams of butter for first two days at this over dose level of boost.
I just completed the PB measurements for the half hour after fifth day of using 3dl of oil + 25 g of butter, with no ill effects. I. e. when part of the prior concentration in the blood had already fallen significantly. - I seem to be at a steady level of concentration inside the cells now. I. e. an inside the cells half life of three days is about correct. - My "accidental discovery."
Here is the data for the fifth day of using 3dl + 25 g swallowed at 9:00 PM in a 50/50 with water emulsion with no food eaten after 7PM:
8:58 BP = 147x84 due in part to 2+ minutes of vigorous shaking of the boost dose with equal volume of water to make an emulsion.
9:03 BP = 134x87
9:12 BP = 126x81 This is a too low variation, I think. The cuff of my G.Tech BP measuring machine may have shifted during the measurement. I know cuff placement can make this difference.
9:18 BP = 132x85
9:29 BP + 124x78mmHg
So I will continue this boost until data from blood to be taken on 15 April 2016 is known but I think, I have discovered “MY max safe boost.” MY is in Caps, as everyone is different. If you have CRPC, you must find your own “max safe boost” NOT copy mine but perhaps can do that in less than the 100 days I took. I speculate that it may be possible to make one 120 pill bottle last a year by taking the 5dl over dose for one day, then taking no pills for two days, but will not test this for at least a year as I soon will start 35 days of IMRT that should kill the target tumor and drive my PSA down to near zero. I will not use Zytiga, while this is done, as measuring PSA is one way they see if the radiation, 2Gy per day, is working.
* For this and more facts, see: Journal of Clinical Oncology, Vol 30, 2012 Feb 13, 2012 which is reply by five Janssen employees to:
MJ Ratain's late 2011 article: Flushing oral oncology drugs down the toilet. in J Clin Oncol Vol 29 pages 3958-3959.
