(T1130-03-19) Ultrasensitive LC-MS/MS Method Enables a Thorough Pharmacokinetic Investigation of Low-Dose Semaglutide Following Oral and Subcutaneous Administration in Healthy Subjects

Purpose: With the dramatic increase in the use of semaglutide for both prescribed and off-label purposes, there is a need for an understanding into the disposition of the different formulations that are available. In this study, the pharmacokinetics and comparative bioavailability of semaglutide following the administration of oral (PO) and subcutaneous (SC) doses in healthy subjects were evaluated.

Methods: Twenty-two healthy subjects were administered either 0.25 mg SC or 3 mg PO and blood samples were taken up to 504 hours following administration. 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 fully characterized following the administration of low subcutaneous and oral doses (see table 1 and figure 1). The bioavailability (PO relative to SC) was 0.66% at the doses administered. In this study we were able to fully characterize the pharmacokinetics of semaglutide of these formulations at lower doses (SC dose of 0.25 mg; PO dose of 3 mg) than what others have evaluated by utilizing a validated bioanalytical method with a lower limit of quantitation. Overall, the study drug was well tolerated, and no serious adverse events were reported.

Conclusion: The bioavailability of semaglutide following oral and subcutaneous administrations has been determined using a sensitive and validated bioanalytical method. This method will enable more thorough 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.


Figure 1: Mean concentration versus time profile of oral and subcutaneous semaglutide


Table 1. Pharmacokinetic parameters of Semaglutide Following Oral and Subcutaneous Administration in Healthy Subjects