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Post by figglebird on May 2, 2019 13:44:03 GMT -5
So pardon my ignorance but re a broad range of potential apis that can be formulated via ts- can anyone explain how uniform that process is particularly w properties like bioavailability... does the differentiation of apis present different properties in ts formulations and therefor the inhalation process?
How customizable or perfectly uniform is formulation and inhalation regardless?
I guess I always presumed that TS could be built to predictive scale but after listening to lqda call and questions ab pharmadynamics I am really curious how if at all possibke it would be to replicate an analogue like Trepostinil so that the pharmadynamics were equivalent to human insulin.
And therfor be readily useable w dreamboat or cricket etc.
thanks for any feed back.
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Post by harryx1 on May 2, 2019 13:56:41 GMT -5
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Post by figglebird on May 2, 2019 14:08:21 GMT -5
Thanks Harry,
The LQDA guy got a question about bioavailability that he obviously backed away from until later etc... but kept seem to point out FDA standards not being as stringent... This is going to be about tech.
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Post by matt on May 2, 2019 14:38:01 GMT -5
The chemistry is different for every molecule or protein so to is the kinetics. You can't assume that the "rapid in and rapid out" dynamics seen with Afrezza will be observed for other drugs just because they are inhaled, with or without TS as a carrier particle. Drugs that can be formulated for TS delivery will, in theory, reach the bloodstream as quickly as Afrezza does but some drugs are not drugs at all but rather "prodrugs" that must undergo an additional chemical change inside the body to become active. This activation can be almost instantaneous, or it can take some time, but in any case it is highly variable depending on the drug. Similarly, how long a drug remains active in the system depends on how it is eliminated from the body; most drugs are filtered out by the kidneys and are passed in the urine while others are inactivated by the liver and eliminated as stool. In some cases rapid action is desirable, as with insulin, in other cases it is highly undesirable, as with hypertension medications where the need is to control blood pressure 24 hours a day.
So the answer is "it depends". TS is good for rapid delivery into the blood stream, especially those drugs which are delivered in an effective form. What happens after that is largely independent of the delivery method.
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Post by harryx1 on May 2, 2019 14:47:52 GMT -5
The chemistry is different for every molecule or protein so to is the kinetics. You can't assume that the "rapid in and rapid out" dynamics seen with Afrezza will be observed for other drugs just because they are inhaled, with or without TS as a carrier particle. Drugs that can be formulated for TS delivery will, in theory, reach the bloodstream as quickly as Afrezza does but some drugs are not drugs at all but rather "prodrugs" that must undergo an additional chemical change inside the body to become active. This activation can be almost instantaneous, or it can take some time, but in any case it is highly variable depending on the drug. Similarly, how long a drug remains active in the system depends on how it is eliminated from the body; most drugs are filtered out by the kidneys and are passed in the urine while others are inactivated by the liver and eliminated as stool. In some cases rapid action is desirable, as with insulin, in other cases it is highly undesirable, as with hypertension medications where the need is to control blood pressure 24 hours a day. So the answer is "it depends". TS is good for rapid delivery into the blood stream, especially those drugs which are delivered in an effective form. What happens after that is largely independent of the delivery method. I guess that's why TreT did so poorly in the Phase 1 trials...  |
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Post by figglebird on May 2, 2019 16:47:25 GMT -5
The chemistry is different for every molecule or protein so to is the kinetics. You can't assume that the "rapid in and rapid out" dynamics seen with Afrezza will be observed for other drugs just because they are inhaled, with or without TS as a carrier particle. Drugs that can be formulated for TS delivery will, in theory, reach the bloodstream as quickly as Afrezza does but some drugs are not drugs at all but rather "prodrugs" that must undergo an additional chemical change inside the body to become active. This activation can be almost instantaneous, or it can take some time, but in any case it is highly variable depending on the drug. Similarly, how long a drug remains active in the system depends on how it is eliminated from the body; most drugs are filtered out by the kidneys and are passed in the urine while others are inactivated by the liver and eliminated as stool. In some cases rapid action is desirable, as with insulin, in other cases it is highly undesirable, as with hypertension medications where the need is to control blood pressure 24 hours a day. So the answer is "it depends". TS is good for rapid delivery into the blood stream, especially those drugs which are delivered in an effective form. What happens after that is largely independent of the delivery method. |
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Post by figglebird on May 2, 2019 16:56:52 GMT -5
Thanks Matt - if its highly dependent on the drug as you point out in terms this potential mini metaorphisis,your conclusion as to ylys only being suitable for rspid acting agents and further thoughts on inhalation does not really add up - respectfully.
Also, from the basic data I am seeing on dpi print trep, inhaled through a generic inhaler, the affect appears like mnkd p1 to replicate the endurance of tyvasso(also inhaled) but do so w less work/dosing abd higher dosing.
Ultimately I took the tie to revisit the revised summarization of TS on the web site.
And on that note alone - i am so impressed.
TS is the near future - if time allows.
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Post by ktim on May 2, 2019 17:14:00 GMT -5
Based on what I know about the manufacturing process, some detail but not a great deal, it would probably be done simply by manufacturing two different API loaded TS powders and then mixing the powders in the correct ratio before filling inhaler/cartridge. No more than educated guess though. |
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Post by peppy on May 2, 2019 22:00:52 GMT -5
The chemistry is different for every molecule or protein so to is the kinetics. You can't assume that the "rapid in and rapid out" dynamics seen with Afrezza will be observed for other drugs just because they are inhaled, with or without TS as a carrier particle. Drugs that can be formulated for TS delivery will, in theory, reach the bloodstream as quickly as Afrezza does but some drugs are not drugs at all but rather "prodrugs" that must undergo an additional chemical change inside the body to become active. This activation can be almost instantaneous, or it can take some time, but in any case it is highly variable depending on the drug. Similarly, how long a drug remains active in the system depends on how it is eliminated from the body; most drugs are filtered out by the kidneys and are passed in the urine while others are inactivated by the liver and eliminated as stool. In some cases rapid action is desirable, as with insulin, in other cases it is highly undesirable, as with hypertension medications where the need is to control blood pressure 24 hours a day. So the answer is "it depends". TS is good for rapid delivery into the blood stream, especially those drugs which are delivered in an effective form. What happens after that is largely independent of the delivery method. Rule of thumb? If the medication is delivered IV, TS is a good candidate?  Treprostinil. REMODULIN® (treprostinil) Injection, for subcutaneous or intravenous use www.remodulin.com/downloads/remodulin-prescribinginformation.pdf |
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Post by lakon on May 5, 2019 5:52:12 GMT -5
harryx1 I recall a patent about this, and I think the answer is a resounding YES as long as the molecules do not have any adverse chemical interactions with one another. mango might be able to point you towards MannKind's associated patent(s).
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Post by anderson on May 6, 2019 7:43:31 GMT -5
harryx1 I recall a patent about this, and I think the answer is a resounding YES as long as the molecules do not have any adverse chemical interactions with one another. mango might be able to point you towards MannKind's associated patent(s). I don't think you need multiple molecules per TS batch, that could be quite complex to make sure you get the correct density of each drug. Simply making a batch of A and a batch of B and accurately measuring how much of A and how much of B you put into a cartridge should suffice and be much easier to do. The question then becomes how much powder is the max you can put into one cartridge.( and if you have room drug C, D, E and F) |
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