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he following message was posted to: PharmPK
Hello Forum.
I am curious to know if anyone has data on which compounds are well
absorbed by the sublingual route so as to find patterns that could
help predict them from their molecular characteristics.
I have done studies on fentanyl and zolpidem and found that they are
surprisingly well absorbed by that route. The zolpidem example is
particularly important because it will enable a low dose to be used
for its effects in brain damage while avoiding excessive sedation and
there may be other useful applications for other compounds. The rapid
onset of effects compared with the oral route will be crucial in
helping patients to control the dose-response effect.
Andrew Sutton
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The following message was posted to: PharmPK
Nitroglycerin is a classic - see part of package insert from Pfizer's
Nitrostat
Pharmacokinetics and Drug Metabolism Absorption: Nitroglycerin is rapidly
absorbed following sublingual administration of
Nitrostat tablets. Mean peak nitroglycerin plasma concentrations occur at a
mean time of approximately 6 to 7 minutes postdose (Table 1). Maximum plasma
nitroglycerin concentrations (Cmax) and area under the plasma
concentration-time curves (AUC) increase dose-proportionally following 0.3 to
0.6 mg Nitrostat. The absolute bioavailability of nitroglycerin from
Nitrostat tablets is approximately 40% but tends to be variable due to
factors influencing drug absorption such as sublingual hydration and mucosal
metabolism.
Dave
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The following message was posted to: PharmPK
Andrew,
It is easier to work backwards from approved drugs by examining the data
that is presented in the Summary Basis for Approval (SBAs) when a drug
application is approved. There is typically good data provided.
Other approved drugs to look at:
Lorazepam (some other tricyclics)
Buprenorphine-naloxone combinations
Nitroglycerin
Furosemide
Morphine (other opiates)
Asenapine
Isosorbide dinitrate
There are reports of experimental formulations for NSAIDS and
tacrolimus.
Good Luck
V. Lee
Chief Executive Officer and Chief Scientific Officer
Adesis Inc.
New Castle, DE 19720
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Andrew: In general drugs with high water solubility and high permeability and
therapeutically effective at low dose come to mind as sublingual candidates. Low
molecular weight (say<500) and low topological polar surface area (computed) also come to
mind as positive attributes. =46rom the pH partition hypothesis one might look to
formulate the drug at a pH that favours presence of the free base form of a basic drug or
perhaps as an ion pair. So we may have to inspect the physicochemical characteristics of
the functional groups ( e.g. ionization constants)
One wonders if nicotine is the champion.
Additionally, assuming the drug as API is active, if it has a high first pass effect (to
inactive metabolites) in the liver then the s/lingual route is favoured.
Hope these comments help;
Angus McLean
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