The pharmacokinetics and comparative bioavailabilty of oral and subcutaneous semaglutide in healthy volunteers

Mohammed Bouhajib; Zia Tayab; Chantal Di Marco; Dennis (Dong-Kyun) Suh

doi:10.1515/jbcpp-2025-0026

Article

The pharmacokinetics and comparative bioavailabilty of oral and subcutaneous semaglutide in healthy volunteers

Mohammed Bouhajib , Zia Tayab , Chantal Di Marco and Dennis (Dong-Kyun) Suh

Published/Copyright: May 26, 2025

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 36 Issue 2-3

Abstract

Objectives

In this study, the comparative bioavailability of semaglutide following the administration of oral (PO) and subcutaneous (SC) doses in healthy subjects was evaluated. The pharmacokinetics of semaglutide of these formulations at lower doses (SC dose of 0.25 mg; PO dose of 3 mg) was examined by utilizing a sensitive bioanalytical method.

Methods

Twenty-two subjects were administered either 0.25 mg SC or 3 mg PO and blood samples were taken up to 504 h. The samples were assayed for semaglutide with an analytical range of 0.05–50 ng/mL. The pharmacokinetic parameters were estimated using a non-compartmental approach and were used to evaluate the comparative bioavailability of semaglutide.

Results

The pharmacokinetics of semaglutide was characterized following the administration of low subcutaneous and oral doses. The comparative bioavailability (PO relative to SC) was 0.66 % at the doses administered. Overall, the study drug was well tolerated, and no serious adverse events were reported.

Conclusions

The bioavailability of semaglutide following oral and subcutaneous administrations has been determined using a validated bioanalytical method. This method will enable more investigations into the pharmacokinetics of all formulations of semaglutide at lower doses, which will enable a better understanding of its’ disposition in healthy subjects and in patients.

Keywords: pharmcokinetics; bioavailablity; subcutaneous; bioanalytical method

Corresponding author: Zia Tayab, Pharma Medica Research Inc, 6100 Belgrave Road, Mississauga, ON, L5R 0B7, Canada, E-mail: ztayab@pharmamedica.com

Research ethics: IRB approval was obtained on July 8, 2021. Study ID: 2021-5043. The study was conducted in accordance with the Declaration of Helsinki.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2025-01-29

Accepted: 2025-04-23

Published Online: 2025-05-26

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2025-0026

Keywords for this article

pharmcokinetics; bioavailablity; subcutaneous; bioanalytical method