Cialis (Tadalafil) steady-state blood level literature

[busgalloway]

This paper is from 2010, but I'd like to draw attention to it as steady-state has been emphasized in threads about HRT.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939761/

Here are some things covered in this study:

1. Steady state of tadalafil is reached after 5 days. This is probably why the Cialis website notes 4-5 days as being when you should see daily low dosages take effect.

2. Steady state tadalafil plasma concentration is 1.6 times higher than that of a single dose.

3. Tadalafil 5mg once a day leads to steady state trough of 55 ng/mL, which corresponds with 90% PDE5 inhibition in vitro, which is the therapy standard likely to produce erections in most men.

4. It is recommended to not consume grapefruit, especially when on a daily dose protocol. It slows the excretion of tadalafil. The study suggests either on-demand exclusively and avoiding grapefruit before taking it, or the lowest possible daily dose(2.5mg once daily).

Based on what I know about grapefruit kinetics in the liver, liver processing of some pharmaceuticals will be slowed for 24 hours. If you use tadalafil on-demand and you have grapefruit or juice, wait at least 24 hours before taking a dose.

Also, others on the forum have also suggested splitting the dosage of tadalafil and taking once every 12 hours. Compared to a single daily dose, this would raise the trough level, but lower the peak for a more regular plasma concentration.

 

[Saul]

Great info. Thanks for posting.

 

[Vince Carter]

Thats great info...Thanks!

 

[Vince]

I agree, very good information. Thanks

 

[Nelson Vergel]

Busgalloway,

I want to thank you for your recent post on steady-state serum levels and Tadalafil. Excelmale strives to remain the leading, online men's health community by providing members with verified, cutting-edge information. Studies such as this are particularly valuable.

Your efforts are appreciated. I am glad you are part of our team.

 

[busgalloway]

Thanks everybody. I should also mention that tadalafil's pharmacokinetics are linear. We tend to take this for granted, but not all medications are that simple.

In other words, doubling the dosage of tadalafil will double its plasma concentration. The excretion has a steady rate, so in half the time it takes to excrete all of it, the plasma concentration will halve. Makes sense right?

Well Viagra (Sildenafil Citrate) doesn't share this feature; after its initial spike in concentration, it is excreted through the body at a rate that looks like exponential decay. Food effects mostly dampen the initial concentration spike for the first 4 hours. Levitra (Vardenafil) also has a non-linear decay similar to Viagra, and research has been ongoing for a decade to eventually offer nebulizers as a form of vardenafil therapy, for faster onset and faster excretion to reduce side-effects.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874258/
https://www.sciencedirect.com/science/article/pii/S1743609516300893

 

[Saul]

Adding to this thread on Tadalafil (Cialis), has anyone found or can they find any studies that show the risks associated with long term use or short term use.

I found this study which did not find any major risks.
https://www.ncbi.nlm.nih.gov/pubmed/15036680
There were no clinically significant laboratory or electrocardiographic findings or changes in vital signs in mean baseline-to-endpoint analysis attributable to tadalafil. Tadalafil administration was not causally associated with drug-induced hepatotoxicity, neutropenia, thrombocytopenia, or renal dysfunction.

Side effect - There is a risk for visual disturbances and optic damage in a small # of cases.

This study seems to refute the skin cancer link.
https://academic.oup.com/jnci/article/109/8/djx086/3835765

Study indicating risk with tadalafil use after prostrate surgery.
https://www.medscape.com/viewarticle/838783

Mixed findings
https://blogs.scientificamerican.com/news-blog/could-cialis-help-treat-some-cancer-2009-05-04/

I did not find a lot of information about risks.

 

[busgalloway]

There were two other papers from 2016 that agree with the study you posted from 2017 that shows a lack of evidence that sildenafil citrate and other PDE5 inhibitors, including tadalafil and vardenafil cause melanoma. Pottegård posited that increase in health-care contact led to early detection of the disease. Lian found that this small increase in melanoma correlates with patients that have over 7 prescriptions or take over 25 pills, but claims more validation is needed to prove it.
https://www.nature.com/articles/bjc2016248
https://www.ncbi.nlm.nih.gov/pubmed/27178449
https://jamanetwork.com/journals/jama/fullarticle/2338254

A paper from this year shows tadalafil causes a lowering of the threshold for myoclonic seizures in mice, but only at at the highest dose of 20mg/kg. It also seems to lower the efficacy of the anticonvulsant oxcarbazepine, but raises it for clonazepam.
https://link.springer.com/article/10.1007/s12640-018-9876-4

I haven't seen much other literature risks other than these besides the side effects themselves.
There are many papers showing no cardiovascular harm from tadalafil, rather many show more benefits. I think the following paper describes each kind of effect, as well as explaining how the initial scares about these effects turned out to be because patients who already had cardiovascular disease were the ones that sought the aid of PDE5i prescriptions.
https://www.tandfonline.com/doi/full/10.1517/14740338.7.1.43

 

[Nelson Vergel]

I pulled some PK graphs from this reference:
Wrishko R, Sorsaburu S, Wong D, Strawbridge A, and McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med 2009;6:2039–2048.

Tadalafil (Cialis) Blood Level After 1 Dose of 20 mg



Tadalafil Blood Levels After A Few Days of 5 mg/day



Comparison Between Different Doses of Tadalafil



Conclusion:

5 mg/day gives you an average tadalafil concentration at day 5 equivalent to the blood concentration at hour 26-30 after one single 20 mg dose. As we all know anecdotally, most men who benefit from tadalafil are able to enjoy improved erections even after 48 hours of administration due to the drug relatively long half-life. So, 5 mg per day may work for men who benefit from a sporadic single 20 mg tadalafil dose while giving coverage every day for potential stable erectile function.

Too bad some of us have side effects like heartburn, backache, headaches, sinus congestion, and flushing.

 

[Nelson Vergel]

"Although the clinical relevance is not entirely clear, a single 20-mg dose has been shown to produce detectable electroencephalographic changes in up to 34% of healthy men.59"



Neurol Res. 2009 Apr;31(3):313-5. doi: 10.1179/174313209X382548. Epub 2008 Nov 25.

EEG abnormalities during treatment with tadalafil, a phosphodiesterase type 5 inhibitor.

Okuyucu EE1, Guven O, Duman T, Gorur S, Melek IM, Akcin S, Yilmazer S.



Abstract

OBJECTIVE:

Tadalafil is a selective phosphodiesterase type 5 (PDE-5) inhibitor approved for the treatment of erectile dysfunction. Less is known about the electroencephalography (EEG) effects of PDE-5 inhibitors, and the present study, therefore, examined the risk of EEG abnormalities associated with tadalafil.

METHOD:

EEG recordings from 35 erectile dysfunction patients taking tadalafil (20 mg) were graded for severity of EEG abnormalities (at admission, 2 and 48 hours after tadalafil administration).

RESULTS:

At admission, there were no EEG abnormalities. At second EEG, abnormalities occurred in 12 (34.3%) of the 35 patients. Eight (22.9%) patients had mild and four (11.4%) patients had moderate EEG abnormalities. At third EEG, one (2.9%) patient had mild and one (2.9%) patient had moderate EEG abnormalities.

CONCLUSION:

PDE-5 inhibitors may produce EEG abnormalities. Although the exact role of PDE in altering susceptibility to seizure remains unclear, epileptic seizures may occur during treatment with PDE inhibitors.

 

[charile12]

I take 3mg Cialis SR from empower. I started taking 2 of them.
I am confused because these are slow release. If I take 3mg SR it seems like I would not get the full effect of it since it's SR. If it's immediate release I know my serum levels peak within 2hours or so.

I ask because an thinking of doing the 7mg SR daily empower has. It's cheaper than taking 2x 3mg. Am I better of taking a 5.5 mg daily immediate release that I can get locally?

Thanks.