Is the effect of sildenafil on Alzheimer’s disease plausible? A pharmacokinetic perspective
There have been many reactions to the retrospective study identifying sildenafil (Viagra) as a candidate drug for Alzheimer’s disease that has just been published in Nature Aging. Despite alternative explanations (and hidden unknowns) the results are generally viewed as enough evidence of an association to justify prospective studies.
One issue that I have not seen mentioned is that of pharmacokinetic (im)plausibility. Sildenafil users do not generally take the drug daily. The patterns of use of sildenafil among commercially insured adults in the United States have been reported in the International Journal of Impotence Research (Delate et al., 2004) (1). The mean number of tablets dispensed over a period of 9 months ranges between 21 and 23 tablets or approximately between 2 and 3 tablets per month.
Sildenafil pharmacokinetic half-life is 4 hours, and its physiological effects last a few hours, not a week. It remains in your system for around 24 hours. That is it. I find it highly improbable that sildenafil itself could have residual biochemical effects that block the damaging processes that occur in Alzheimer’s disease long after there is no detectable drug in the body.
Incidentally, the results obtained in cell culture experiments with nerve cells derived from Alzheimer’s disease patients used concentrations of the drug around 100 times those achieved by taking the pill.
I wonder what dosing regimen one should use in prospective studies. The solution may be to select a real-life-like usage and a daily dosage.
(1) https://doi.org/10.1038/sj.ijir.3901191
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