Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

Abstract

Purpose: The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin.

Methods: Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC_0-∞), (AUC_0-t); C_max; t_max; t_½, k_e; k_a were measured using validated LC-MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin.

Results: Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7-142.3) for AUC_0-t, and 167.6% (154.6-181.8) for C_max. On the other hand, sildenafil pharmacokinetics were not affected. G_max changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUC_g0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs.

Conclusion: Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered.

Registration: This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019.

Keywords: Diabetes; Drug interactions; Pharmacodynamics; Pharmacokinetics; Saxagliptin; Sexual dysfunction; Sildenafil.