drug developers

[epidural man]

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So imagine you create a drug/system/liposome that can elute a drug of your choice over a certain amount of days of your choice.

Now imagine you decide that you are going to place a local anesthetic in that liposome. You go to the shelf of local anesthetics and take a look at them all to decide which one you will choose....and you SHOULD be thinking "duration of action shouldn't come into play since I COMPLETELY CONTROL duration of action, so what I MOST care about is safety profile and therapeutic index and side effect profile. That is all that matters."

That is how that thought process should work.

And I have always been baffled how ridiculous it was that the folks who were first to market with a liposomal local anesthetic somehow decided to choose the most neurotoxic, cardiotoxic, and lowest therapeutic index LA on the shelf. Could there have been a worse decision made that day?

Okay...so be it. The folks that invented Exparel are idiots. Accept it and move on. Let's hope that scientists in the lab who come up with new extended release LA's are somewhat more enlightened. In fact, they don't even have to be smart. They just have to be - not REALLY REALLY STUPID.

Yet....guess what?

The newest extended release product (HTX-011) has bupiviciane in it as well. I cannot freakin' believe it. I just can't.....

What the?

 

[epidural man]

Here is something about how incredibly and unbelievable obtuse the inventors of Exparel are (and Heron Therapeutics).

If I want to use LIDOCAINE - a much safer LA with higher therapeutic index then Bupivicaine - with Exparel, I can't. Why? Because the much safer LA has a higher affinity to sit inside the liposome than the much more dangerous LA and it displaces the extremely toxic and dangerous LA.

Don't you think that fact alone would have given the lab geek a clue as to what LA he should probably place in the liposome? Why not start with the safe one and NOTHING anyone could do would make it any more dangerous?

It seriously is just so unbelievable.

 

[nimbus]

Could it be that they knew liposomal technology doesn’t make that much difference so they knew they had to start with something already long acting?

 

[pgg]

So, uh, you're not a fan any more?

Edit - maybe I'm misremembering but I thought you had a near-BladeMDA level of love for Exparel. 🙂 Hence my question.

 

[Urzuz]

How do you know lidocaine chemically can be carried in a liposomal delivery system? Or how it may be challenging to manufacture such a drug? Granted bupivacaine and lidocaine are in the same class of drugs, I don't think you can assume anything. I'm not a chemist and admittedly you aren't either, so without knowing that it's possible to do so and/or the challenges associated with it, I don't think you should jump to conclusions.

That being said, Exparel is useless and you should stick to using plain bupivacaine.

 

[epidural man]

So, uh, you're not a fan any more?

Edit - maybe I'm misremembering but I thought you had a near-BladeMDA level of love for Exparel. 🙂 Hence my question.

Still a fan...

I've always been pissed they used bupivacaine - and now even more so that a NEW company made the same stupid mistake.

 

[epidural man]

How do you know lidocaine chemically can be carried in a liposomal delivery system? Or how it may be challenging to manufacture such a drug? Granted bupivacaine and lidocaine are in the same class of drugs, I don't think you can assume anything. I'm not a chemist and admittedly you aren't either, so without knowing that it's possible to do so and/or the challenges associated with it, I don't think you should jump to conclusions.

That being said, Exparel is useless and you should stick to using plain bupivacaine.

Yes, I actually am a chemist.

But regardless - yes, it can carry lidocaine. it can carry anything they want (I'm sure with some limitations). In fact, if you use lidocaine with Exparel, the lidocaine PREFENTIALLY displaces the bupivacaine and the liposome CARRIES the lidocaine. The depofoam technology originally carried morphine.

In fact, years ago they ask several physicians what they thought would be most impactful as a long acting medication.

Also, your point about Exparel being useless isn't relevant and there are plenty of other threads expressing that same opinion.

 

[facted]

Well, if you're looking for longest acting, than bupi inside of a liposome is still going to last longer than lidocaine inside a liposome. Who knows to what extent. In fact, who knows how long bupi lasts inside there.

You could argue they could use something like ropi with a smaller cardiac toxicity, but to be honest, I've yet to hear of a exparel induced cardiac event, so I'm not sure what problem we're really discussing.

 

[epidural man]

Well, if you're looking for longest acting, than bupi inside of a liposome is still going to last longer than lidocaine inside a liposome. Who knows to what extent. In fact, who knows how long bupi lasts inside there.

You could argue they could use something like ropi with a smaller cardiac toxicity, but to be honest, I've yet to hear of a exparel induced cardiac event, so I'm not sure what problem we're really discussing.

Cardiotoxicity isn't the only issue - although that is super important.

But let's say they used a drug that is very potent, works extremely fast, and has a HUGE therapeutic index - say....2-chloroprocaine. There would be several very important clinical reasons that would give the clinician benefit to having a drug with a much larger therapeutic index be used.

Take for example the failed TAP block with a extended delivery system drug like HTX-011. What do you do now if you have given a large bolus of bupiviciane (even if it is tied up in a liposome vehicle)?

Well if you have tons of head room - it isn't an issue.

 

[epidural man]

Well, if you're looking for longest acting, than bupi inside of a liposome is still going to last longer than lidocaine inside a liposome. Who knows to what extent. In fact, who knows how long bupi lasts inside there.

You could argue they could use something like ropi with a smaller cardiac toxicity, but to be honest, I've yet to hear of a exparel induced cardiac event, so I'm not sure what problem we're really discussing.

Also, the LONG ACTING comes from the technology of depofoam, NOT the chemical it carries inside it. They can create the depofoam to last as long as they want (from what I understand). So there is absolutely NO NEED to carry a long acting drug inside. That is the whole point.

The point about them thinking that it doesn't actually work and so they need to mask the failed technology with along acting local would make a useful argument - but I believe THEY believe it actually works. (They have some good data comparing Exparel with straight bupivacaine I have seen. It's impressive enough to believe it works - regardless of the huge majority of nay-sayers here. We will wait and see...BUT...all you nay-sayers need to NOT be hypocrites and stick to your guns. If you say it doesn't work - stick to it. DO NOT betray your belief. Hold fast to your thoughts forever and ever. )

 

[pgg]

 

[facted]

Also, the LONG ACTING comes from the technology of depofoam, NOT the chemical it carries inside it. They can create the depofoam to last as long as they want (from what I understand). So there is absolutely NO NEED to carry a long acting drug inside. That is the whole point.

The point about them thinking that it doesn't actually work and so they need to mask the failed technology with along acting local would make a useful argument - but I believe THEY believe it actually works. (They have some good data comparing Exparel with straight bupivacaine I have seen. It's impressive enough to believe it works - regardless of the huge majority of nay-sayers here. We will wait and see...BUT...all you nay-sayers need to NOT be hypocrites and stick to your guns. If you say it doesn't work - stick to it. DO NOT betray your belief. Hold fast to your thoughts forever and ever. )

I don't know the actual chemistry involved here, so I don't know if you're accurate in saying they can make the drug last as long as they'd like.

And we've beaten this horse to death already, but there is a LOT of exparel vs. bupi data that is NOT impressive. Regardless, I think they chose bupi because it lasts a heck of a long time even after it leaches out of the liposome and I think that's their goal.