Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

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.