Regarding dosage, starting from “The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs” (2015) http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/full
A single dose of D+Q (D: 5 mg kg−1 body weight and Q: 50 mg kg−1 by oral gavage here and in the following studies), a drug ratio that was most effective in senescent MEFs (data not shown), reduced SA-βgal+ cells (Fig. 3C) and p16 mRNA (Fig. 3D) in fat from old mice within 5 days. D+Q also reduced p16-positive cells in liver from old mice (Fig. 3E-F). As with AP20187, the drug that activates selective killing of cells expressing p16 in transgenic INK-ATTAC mice (Baker et al., 2011), not all senescent cells were removed by D+Q.
A direct scaling of this 5 mg/kg body weight dose of dasatinib to my weight gives (5 mg/kg)(70 kg) = 350 mg.
This dose is twice the “escalation dose” recommended for cancer treatment in humans and is unsafe.
The Human Equivalent Dose (HED) scaling from mice to 70 kg adult humans is
http://www.fasebj.org/content/22/3/659.full.pdf+html
(5 mg/kg)(3/37)(70 kg) = 28.4 mg
I did not see much if any benefit at 70 mg Dasatinib + 6400 mg Quercetin dihydrate.
Increasing the dose to 120 mg Dasatinib + 6400 mg quercetin and adding 2000 mg honokiol cleared some of the sun/age damage to my skin.
For further confirmation, from the plasma concentration-time profile shown in Figure 1 of “Metabolism and Disposition of Dasatinib after Oral Administration to Humans” (2008) http://dmd.aspetjour...t/36/7/1357.ful, a 100 mg dose of Dasatinib results in a peak serum concentration of 104.5 ng/ml after 0.5 hr with a half-life of 3.6 hours. Converting to moles/liter, this peak concentration is calculated to be
= (104.5 ng/ml)/(488.01 ng/nMol)
= 0.214 nM/ml
= 214 nM/l, which is close to a reasonable target of 200 nM/L taken from Figure 2A of “The Achilles’ Heel”
Here is what I currently take: on an empty stomach I ingest
- 120 mg Dasatinib
- 2000 mg Quercetin phytosome
- 2000 mg Honokiol (Magnolia bark extract)
- 500 mg Pterostilbene
- 600 mg Sodium butyrate every 15 minutes, 8 total, starting 15 minutes before taking anything else
I am certain that there is a strong apoptotic effect from this combination since my skin has gotten progressively smoother with repeated doses and some keratoses have either disappeared or been greatly reduced.
The major side effects I experience is fatigue and less mental clarity, which lasts maybe 5 days. On two occasions there was diarrhea.
Dasatinib is a powerful drug that is not without side effects or interactions.
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“Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors” (2009) http://clincancerres.aacrjournals.org/content/15/19/6232.short
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http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/cancer-drugs/dasatinib
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http://www.drugs.com/cdi/dasatinib.html
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http://en.wikipedia.org/wiki/Dasatinib
Side effects and contraindications include
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Do not take dasatinib if you are sick. Dasatinib increases the risk of getting an infection from a drop in white blood cells – it is harder to fight infections and you can become very ill. You may have headaches, aching muscles, a cough, a sore throat, pain passing urine, or you may feel cold and shivery.
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30% develop diarrhea
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30% experience headaches
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20% develop a rash or red, dry, itchy skin
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20% experience fluid buildup in the body
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20% experience a feeling of being sick
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20% experience fatigue
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10% feel bone and muscle pain
