Which peptides can be absorbed sublingually?

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Last updated: July 7, 2025View editorial policy

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From the Research

Desmopressin is a peptide that can be absorbed sublingually, as demonstrated by a study published in 2006 1, which found that a sublingual dose of 240 microg resulted in a pharmacokinetic profile comparable to 20 microg administered intranasally. This is further supported by a more recent study from 2023 2, which developed a new sublingual formulation for transmucosal delivery of peptides, including desmopressin. Other peptides that can be absorbed sublingually include insulin, calcitonin, oxytocin, and certain GLP-1 agonists, which are typically small in size and have specific physicochemical properties that allow them to penetrate the sublingual mucosa. For effective sublingual absorption, peptides should ideally be lipophilic or have a balance between hydrophilic and lipophilic properties. The sublingual route bypasses first-pass metabolism in the liver, which can significantly degrade peptides when taken orally, and works because the sublingual area has a thin epithelial membrane, rich blood supply, and relatively neutral pH environment compared to the stomach. However, absorption efficiency varies widely among different peptides, with many requiring absorption enhancers or specialized delivery systems to improve bioavailability. Patients using sublingual peptides should place them under the tongue and avoid swallowing saliva immediately to maximize absorption through the mucous membranes. Some key points to consider when administering peptides sublingually include:

  • The size and physicochemical properties of the peptide
  • The use of absorption enhancers or specialized delivery systems
  • The importance of proper administration technique to maximize absorption
  • The potential for variability in absorption efficiency among different peptides and patients. It's also worth noting that desmopressin has been used for many years in the treatment of diabetes insipidus, nocturnal enuresis, and nocturia associated with multiple sclerosis, and has been recommended in certain circumstances for the treatment of nocturia in men and women 3. Overall, the sublingual route offers a convenient and effective way to administer peptides, with the potential for improved bioavailability and reduced side effects compared to other routes of administration.

References

Research

[Development of New Sublingual Formulation for Transmucosal Delivery of Peptides].

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2023

Research

Desmopressin for nocturia in adults.

Drug and therapeutics bulletin, 2017

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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