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Hydromorphone has a greater affinity for mu receptors than buprenorphine

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romealone

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Jan 28, 2010
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I was just checking the km values for various opioids and I see that hydromorphones affinity (km of .29) is higher than that of buprenorphine (km of .85). Based on these km values it seems clear that hydromorphone has a higher affinity, and yet I always see warnings here regarding precipitated withdrawal from the use of buprenorphine after hydromorphone. Considering these km values, it seems like bupe would not be able to remove hydromorphone from the receptors to cause precip withdrawal. Am I missing something?
 
I'm pretty positive those numbers are apples and oranges. Probably same receptor but I'd be willing to bet my watch those numbers came from different studies that used different hot ligands.
 
Hmmmm, You guys might be right. I just went to the pdsp website and under test ligand I put on hydromorphone and checked the km value. I then did the same for buprenorphine and noticed that the km for hydromorphone was significantly lower, suggesting a much higher affinity. I am ignorant as to how else I can check the km values to compare these compounds. You mention they likely have different hot ligands but I don't know how to account for this. Can anyone who is better versed in this compare the affinities and post the results and/or illuminate me as to where am going wrong when looking up these values. Thanks
 
Try and compare values from the same study, if possible. Looking at it, there's a result for each by Wentland MP, both published in 2009, but the ref links seem to be broken so I can't tell if it's the same study and can't easily find it. But those values are hydromorphone: 0.28nM, and buprenorphine: 0.21nM, so pretty much the same.

The difference in apparent potency could be due to any of several factors though, rate and extent of absorbtion, distribution of the drug, metabolism, rate of excretion (ADME).
 
Yeah, but if you consider all of those factors, you would still conclude hydromorphone would have higher apparent affinity (faster absorption, higher bioavailability, much shorter half-life).

Strange. Does hydromorphone penetrate the BBB poorly or something else that inhibits it's access to the brain? For a non-tolerant user, an buprenorphine doses start around .2mg. Hydromorphone does start around 2mg. Something doesn't add up but I'm too tired to look into it more right now.
 
Uh BBB penetration comes under distribution.

There's also association/dissociation rate constants; if hydromorphone has a high k(on) and k(off) and bupe has low k(on) and k(off) that could account for the difference.
 
I think skillet has the right idea. Buprenorphine appears to have a very low k(on) and even lower (or nonexistent?) k(off). From Englberger 2006:

"A peculiarity of buprenorphine is its slow receptor binding
kinetics. Despite a very long record of pharmacological data
about buprenorphine covering 3 decades (for review see Cowan,
1995; Johnson et al., 2005), its opioid receptor kinetics, especially
the very slow and incomplete receptor dissociation, are
not well understood. Depending on the experimental models
used, buprenorphine generally showed slow receptor association
in binding assays and more slower, biphasic, or even no
dissociation (Villiger and Taylor, 1981; Boas and Villiger, 1985;
Rothman et al., 1995)"
 
@Jay.. well my tolerance to opiates is about 30 mg oxycodone.. and when at the hospital they iv'd me with 2 mg hydromorphone and I didn't feel a thing except for my facial pain go away.. I then proceeded to go home and snort 12 of them 24 mg and recieved only drowsiness no discernable euphoria whatsoever
 
2mg of hydromorphone sublingual dangerous? I don't think so. According to my quick converter 2mg hydromorphone IV = about 26mg oxycodone ORAL, so sublingual should put that somewhere more like 15-20, perhaps even a little less? I guess I don't have a lot of experience with the drug, but I think 2mg is the smallest tablet they even make.

edit: nope, they make a 1mg tablet as well.
 
A non-tolerant user could dose 4 mg. of Hydromorphone orally without problems, this of course is all subject to different people.

Hydromorphone crosses the BBB very readily due to it's high lipid solubility.
 
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