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

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.