I seem to recall reading something that said there is an effective does of phenylephrine, if you take it by itself, 2x the dose works, but if you take it with other meds, it might be ok by itself. Something about the stomach acid neutralizing it. Might help to take it with food too.
What you’re probably thinking of is topical (is that the right word here?) phenylephrine. If you snort it, like as a nasal spray, and it soaks directly into the inflamed nasal tissue, then it has an effect. Swallowing it does not.
Well there's this report [1] from 2007 that suggests a 25 mg dose works significantly better than the 10mg dose generally available. I'm pretty sure that's not the report I'm recollecting, but it was easy to find.
Possibly a digested version of this report from 2015 [2] which found The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone.
Combining information from the first and second reports, the generally available 10 mg dose isn't very effective, but increasing to 25 mg is much more effective --- and you can double the absorption of 10 mg phenylephrine by also taking 1000 mg of acetaminophen the recommended adult dose of 'extra strength' Tylenol in the US). So take double the dose or with something else (tested specifically with acetaminophen, but anecdotally, seems to also work with ibuprofen), and it may work much better than alone. Given that it's been much easier to obtain phenylephrine than more effective decongestants, it's useful to know what you can try to make it work, if that's all you have.
