Hey Mark,
Thanks for the feedback, I know what you're going through with Diphenhydramine as I've had the same problem. What we're up against deals with the pharmacokinetics of Diphenhydramine.
The time to T
max is listed as 2.6 hours for an oral dose of Diphenhydramine. This is the time needed for an oral dose of Diphenhyramine to reach a maximum serum concentration from ingestion. This is also where Diphenhydramine reaches its maximum therapeutic effect.
The other important number is the Diphenhydramine half-life (T1/2). This is the time from oral dose ingestion to the point in time where the serum concentration has dropped to one half of T
max serum concentration.
That basically leaves us with a window of time between Tmax and T1/2 of 4 to six hours at a therapeutic serum concentration as illustrated in the following graphic.
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There are two ways to maintain a constant therapeutic serum concentration of Diphenhydramine, decrease the dosing interval and increase the dose.
Sooo... Diphenhydramine pharmacokinetics suggest dosing every 4 to 6 hours at 25 mg. This sounds simple... However I've found the dosing interval needs to be 25 mg every 4 hours during the day from wake-up and 50 mg at bedtime..which should give you at least 6 hours of uninterrupted sleep.
I also had to modify the vitamin D3 dosing interval and dose with a maintenance dose of 20,000 IU/day taken with the largest meal of the day along with the cofactors. In addition, I needed an additional 10,000 IU vitamin D3 at bedtime and another 10,000 IU vitamin D3 upon waking up in the morning to remain CH pain free day and night.
The rationale for this vitamin D3 dosing schedule is based on the following graph illustrating the Pharmcokinetics and serum concentrations of vitamin D3 and 25(OH)D3.
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The data I've collected so far indicates both vitamin D3 (cholecalciferol) and 25(OH)D3 both enter target cells within the brain and in particular the trigeminal ganglia where they are further hydroxylated to 1,25(OH)2D3, (Calcitriol), the genetically active vitamin D3 metabolite responsible for preventing CH.
Be sure to see your PCP for lab tests of your serum 25(OH)D, calcium and PTH on a monthly basis until you're able to stop taking the Diphenhydramine and reduce the vitamin D3 intake to a maintenance dose of 10,000 IU/day. In practice, it has taken me up to a month to remain CH pain free where I could stop taking the Diphenhydramine and lower my vitamin D3 dose to 10,000 IU/day.
During that time, my serum 25(OH)D was > 164.7 ng/mL. That didn't concern me or my PCP as long as my serum total calcium remained within its normal reference range of 8.5 to 10.5 mg/dL and my PTH remained at the low end of its normal reference range of 17 to 70 pg/mL.
As a rule, whenever I need to take more than 10,000 IU/day vitamin D3 or my serum 25(OH)D is over 100 ng/mL, I stop taking calcium supplements, avoid calcium rich food types and drink 2 liters of water a day. This helps lessen the calcium load on the kidneys.
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Hope this helps...
Take care and please keep us posted.
V/R, Batch