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The article comes so close to explaining a way to make it work, likely due to his hesitancy to recommend exceeding the recommended dose: > Why is oral phenylep
by PragmaticPulp 5y ago
The article comes so close to explaining a way to make it work, likely due to his hesitancy to recommend exceeding the recommended dose:
> Why is oral phenylephrine so useless? It is extensively metabolized, starting in the gut wall. You can find a bioavailability figure of 38% in the literature, but that appears to be the most optimistic number possible, and you can also find studies that show 1% or less. Overall, the Cmax is highly variable patient-to-patient, and the lack of cardiovascular effects at low doses argues for very low systemic effects (and expected low efficacy as a decongestant). The bioavailability increases at higher doses as you apparently saturate out some of the metabolic pathways, but at the 10mg dose typically used for decongestants, you can forget it.
Phenylephrine has variable Bioavailability. The bioavailability doubles if you take it with Tylenol, which is actually common in the context of colds. (Source: https://pubmed.ncbi.nlm.nih.gov/25475358/ https://pubmed.ncbi.nlm.nih.gov/25475358/ ) The maximum dose was probably chosen based on worst-case scenarios, whereas the average person who complains it doesn't work is probably absorbing much less.
Always consult with your doctor, but I've found that taking a second dose of phenylephrine if the first one hasn't worked within about 30 minutes usually does the trick. Or just take it with Tylenol. It's worth checking your blood pressure to make sure you haven't started entering the realm of side significant side effects, though.
Also I should point out that pseudoephedrine isn't available behind the counter everywhere. It's prescription-only in some places.
- JumpCrisscross 5y agoDo we have a study showing these (second dose within 30 minutes or paracetamol + phenylephrine) performing better than placebo?
- PragmaticPulp 5y agoWe actually have a lot of studies where even standard 10mg phenylephrine taken alone outperforms placebo: https://pubmed.ncbi.nlm.nih.gov/17692721/ https://pubmed.ncbi.nlm.nih.gov/17692721/ Note that Figure 3 also mentions the Tylenol combination effect and even shows how 10mg Phenylephrine + Tylenol performs somewhere between 10mg and 45mg of phenylephrine. The article author just cherry-picked the one study where phenylephrine performed the worst. Cherry-picking a single study to support a conclusion and ignoring meta-analyses would normally get someone torn apart in the HN comments but apparently everyone loves pseudoephedrine so it gets a pass.
- natechols 5y ago"Data from 7 crossover studies involving a total of 113 subjects were reanalyzed and then pooled for meta-analysis" This is a huge red flag - I've read too many of Derek Lowe's blog posts to take that kind of study very seriously as medical advice. Much more promising leads than this have utterly bombed in clinical trials, it happens all the time.
- PragmaticPulp 5y agoRead the whole abstract. They showed which studies reached statistical significance on their own. You could just read those studies and ignore the meta-analyses if you want. I honestly don't understand this current trend of assuming meta-analyses are inherently incorrect and cherry-picking the worst study as the source of the truth.
- natechols 5y agoIt's not the meta-analysis part that's the biggest red flag, it's "a total of 113 subjects". That's the size of a Phase I trial, and the road to Phase III and clinical approval has a crazy high attrition rate.