Fentanyl Vs. Alfentanil in Acidosis

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Fentanyl has a Pka of 8.4 and is 91% ionized at a pH of 7.4. Alfentanil has a PKa of 6.5 and is 11% ionized at a pH of 7.4, and also has a lower volume of distribution than fentanyl. I believe Alfentanil is more lipophillic but don't quote me on that. If a patient is in metabolic acidosis say pH of 7.0 wouldn't the alfentanil become even more unionized

Thanks,

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Fentanyl has a Pka of 8.4 and is 91% ionized at a pH of 7.4. Alfentanil has a PKa of 6.5 and is 11% ionized at a pH of 7.4, and also has a lower volume of distribution than fentanyl. I believe Alfentanil is more lipophillic but don't quote me on that. If a patient is in metabolic acidosis say pH of 7.0 wouldn't the alfentanil become even more unionized

Thanks,

It does depend upon the lipid solubility, but at 6.5 it still may be a weak base. Just because it has a little lower Pka than Fentanyl doesn't nec mean that it will become less ionized in a more acidic condition. You would infact have to know if it is more lipid soluble, etc. But the fact that it is less ionized at the same pH as fentanyl seems like it may be more effective. I hope this helps, but I am not really sure. I would probably ask your question to a PharmD. Good luck

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I could not find the answer either, but did hit these tid-bits:

A unique advantage of alfentanil (over fentanyl) is a more rapid onset of action...is a result of the low pK...nearly 90% of the drug exists in the lipid-soluable non-ionized form at physiologic pH. (baby miller, pg 76)

Fentanyl is significantly bound to RBCs (approx 40%). Plasma fentanyl is highly protein bound (79-87%). Fentanyl protein binding is pH-dependent, such that a decrease in pH will increase the proportion of fentanyl that is unbound. (Barash, pg 358).

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If anyone is curious Fentanyl is more potent in an acidotic state since it becomes more ionized giving more ionized drug available as a ligand.

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