Rapamycin and Grapefruit Juice

[CTStan]

I still must be missing something. Sorry to be dense.

Are we saying that 6mg of rapamycin would ordinarily be expected to give you 6ng/ml in blood at Cmax?

[lsutiger]

So just so I’m clear in order to see if my rap dosing is optimal----on how to do this. I should get sirolimus labs two hours before my weekly rap dose, then two hours afterwards? Thanks for the clarification.

[Agetron]

Yes— you can do your 1st blood draw anytime one week after your last dose.

Take your dose with Grapefruit Juice or not and retest blood I think between 2 or 2.5 hours after your dose is best.

My physician is very easy about setting up my blood draws. I might even do one more set of tests when I see him this week. The sirolimus blood test is taken in a lavender topped blood vial. Make sure they put it in the correct color or it will not get tested.

[Agetron]

Are we saying that 6mg of rapamycin would ordinarily be expected to give you 6ng/ml in blood at Cmax?

That is would I would suppose.

[CTStan]

Thanks. That clarifies the calculation.

But I dont know if that assumption is correct. If there is data somewhere to show the relationship between normal absorption of a given dose of rapamycin with the concentration in plasma at Cmax, that would certainly be something we need to know.

[Agetron]

It is rather tricky - no straight answer on the internet - here is one from Mount Sinai that includes sirolimus - and seems to say 4-20 ng/mL is from a 4-22 dose. Almost one to one - if I am reading this right. 4ng/mL comes from 4mg dose.

Link:https://www.mountsinai.org/health-library/tests/therapeutic-drug-levels

Why the Test is Performed

With most medicines, you need a certain level of the drug in your blood to get the proper effect. Some medicines are harmful if the level rises too high and do not work if the levels are too low.

Monitoring the amount of the drug found in your blood allows your provider to make sure the drug levels are in the proper range.

Drug level testing is important in people taking drugs such as:

• Flecainide, procainamide or digoxin, which are used to treat abnormal beating of the heart
• Lithium, used to treat bipolar disorder
• Phenytoin or valproic acid, which are used to treat seizures or other conditions
• Gentamicin or amikacin, which are antibiotics used to treat infections
• Tacrolimus, sirolimus or cyclosporine, which are used to suppress immune system activity against transplanted organs

Testing may also be done to determine how well your body breaks down the drug or how it interacts with other drugs you need.

Normal Results

Following are some of the drugs that are commonly checked and the normal target levels:

• Acetaminophen: varies with use
• Amikacin: 15 to 25 mcg/mL (25.62 to 42.70 micromol/L)
• Amitriptyline: 120 to 150 ng/mL (432.60 to 540.75 nmol/L)
• Carbamazepine: 5 to 12 mcg/mL (21.16 to 50.80 micromol/L)
• Cyclosporine: 100 to 400 ng/mL (83.20 to 332.80 nmol/L) (12 hours after dose)
• Desipramine: 150 to 300 ng/mL (563.10 to 1126.20 nmol/L)
• Digoxin: 0.8 to 2.0 ng/mL (1.02 to 2.56 nanomol/L)
• Disopyramide: 2 to 5 mcg/mL (5.89 to 14.73 micromol/L)
• Ethosuximide: 40 to 100 mcg/mL (283.36 to 708.40 micromol/L)
• Flecainide: 0.2 to 1.0 mcg/mL (0.5 to 2.4 micromol/L)
• Gentamicin: 5 to 10 mcg/mL (10.45 to 20.90 micromol/L)
• Imipramine: 150 to 300 ng/mL (534.90 to 1069.80 nmol/L)
• Kanamycin: 20 to 25 mcg/mL (41.60 to 52.00 micromol/L)
• Lidocaine: 1.5 to 5.0 mcg/mL (6.40 to 21.34 micromol/L)
• Lithium: 0.8 to 1.2 mEq/L (0.8 to 1.2 mmol/L)
• Methotrexate: varies with use
• Nortriptyline: 50 to 150 ng/mL (189.85 to 569.55 nmol/L)
• Phenobarbital: 10 to 30 mcg/mL (43.10 to 129.30 micromol/L)
• Phenytoin: 10 to 20 mcg/mL (39.68 to 79.36 micromol/L)
• Primidone: 5 to 12 mcg/mL (22.91 to 54.98 micromol/L)
• Procainamide: 4 to 10 mcg/mL (17.00 to 42.50 micromol/L)
• Quinidine: 2 to 5 mcg/mL (6.16 to 15.41 micromol/L)
• Salicylate: varies with use
• Sirolimus: 4 to 20 ng/mL (4 to 22 nmol/L) (12 hours after dose; varies with use)

[CTStan]

Yes it is tricky. In the particular article you cited I read it is a target level expressed as either 4 to 20 ng/mL or as 4 to 22 nmol/L rather than results related to a particular dose.

I might have found something here: Phase 1 Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients - PMC

In one of their charts they show Cmax of 15 ng/ml for 6mg dose with no inhibitor.

So if I’m reading it correctly you are getting about 2x with simultaneous ingestion of 6mg rapa with 5 oz of gfj.

[Agetron]

Hmmmm… how to read this?

[CTStan]

The way I read it is:
At a dose of 6mg, with a sample size (n) of 3 patients, given neither ketoconazole nor GFJ, the Cmax was 15ng/ml. With keto, however, the Cmax was 74.6. That sounds reasonable since there is an expected 5 fold increase in absorption when given with keto.

This is admittedly a pretty small sample and with so much individual variability, I dont know how much credence you can give it.

[Agetron]

Thanks for clarification… still don’t get how to get a handle on dosing with GFJ.

I do know that at 36 ng/mL amounts for 7 months… my biological age took a hit on glycans and Methylation. Lol

Look at that aging bump for 7 months at 36 ng/mL 6mg rapamycin and GFJ… reduced back to 6 mg … no GFJ… and 4 months later better biological age with two different tests.

[BeatTheOdds]

Hi. I was just reading you have occasional problems with insomnia. High histamine foods can cause this in some people. Grapefruit is very high in histamine. Might be worth checking if you feel uncomfortable when trying to sleep after eating foods that are known to cause problems with histamine. An unknown histamine intolerance could also cause problems with stress and anxiety along with a load of other symptoms. Worth thinking about.

[CTStan]

Very puzzling indeed!!

[BeatTheOdds]

Hi. Interesting thread. I just spent the evening reading through it. Thanks to all and especially those posting data like Agetron. Doing great work and such a help.

Unfortunately grapefruit juice doesn’t always agree with me (FODMAPS and histamine). I read rapa can also be enhanced with ketoconazole or Itraconazole, has anybody here tried those and how do they compare to GFJ?

Would be great to save some money on my rapa.

[teadrinker88]

Thanks for the info. Definitely might be related. I actually got a stable supply and cheap supply of rapamycin (from India) and so switched to just taking the dose I needed without grapefruit. I did eventually overcome my severe insomnia. Insomnia is occasional now. Never thought grapefruit might cause sleep issues, but it makes sense.

[johano]

Does it matter what type of GFJ and whether fresh or not?

I am considering mixing it up for safety, i.e. for instance one week 6 mg w/o GFJ, the other week 2 mg with GFJ, in order to compensate for slight deviation in dosage (especially if its too much with GFJ). Any thoughts on that?

[Agetron]

I found that the pasteurized brand Simply - Grapefruit from Wal-Mart works fine.

Some thought it being pasteurized might prevent it from having positive benefits. But, I found on my LabCorp blood test it worked increase the dose… just like fresh squeezed.

Just got use to cutting and squeezing a Red Grapefruit… the taste is not bad. Lol

[DeStrider]

I use two fresh grapefruits eaten 1-4 hours beforehand.

Be wary of Ketocanazole as it is bad for your liver even though you get more bang for the buck. With all the supplements we take, we have to take care of our liver!

I also like the taste of grapefruit better…

[Joseph_Lavelle]

I love grapefruit. Grapefruit has long been a fantastic weight loss tool. It really cuts the appetite.

[RapAdmin]

@DeStrider

I use two fresh grapefruits eaten 1-4 hours beforehand.

I really like the approach of using fresh grapefruit to do this. Agetron’s approach is fine - but I don’t like to drink juice due to sugar content, and so the only time I used the grapefruit juice was every one to two weeks and so the grape juice is getting pretty old after just two dosings.

Fresh grapefruit seem to store well in the fridge… perhaps my imagination, but it seems to store better than the juice.

[Agetron]

Yes, I only used Simply Grapefruit juice a few times a year and a half ago… and Labcorp tested it for potency with rapamycin. It works, but only used it sparingly and it sat in the refrigerator too long. So went fresh GF .

I suggest Simply as an alternative for those who can’t get the fresh real thing.

I exclusively use one big Red Grapefruit each time… cut and hand squeezed… for past year and a half.

I just down my Rapamune pills with the GFJ…
and a bit of pulp.