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 saxaglip...

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Publicado en:European Journal of Clinical Pharmacology Vol. 78; no. 12; pp. 1935 - 1945
Autores principales: Mansour, Rania Y., ElBorolossy, Radwa, Shaheen, Sara M., Sabri, Nagwa A.
Formato: research tables/charts Journal Article
Publicado: Springer Nature Dec2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2022
      vid: 78
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-022-03397-w
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        atl: Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers.
      aug:
        au:
          Mansour, Rania Y.
          ElBorolossy, Radwa
          Shaheen, Sara M.
          Sabri, Nagwa A.
        affil: MScs. Of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
      sug:
        subj:
          Drug Interactions Evaluation
          Hypoglycemic Agents Pharmacokinetics
          Sildenafil Pharmacodynamics
          Safety
          Human
          Sildenafil Administration and Dosage
          Confidence Intervals
          Mass Spectrometry
      ab: 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 (AUC0-∞), (AUC0-t); Cmax; tmax; t½, ke; ka 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 AUC0–t, and 167.6% (154.6–181.8) for Cmax. On the other hand, sildenafil pharmacokinetics were not affected. Gmax changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUCg0-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.
      pubtype: Academic Journal
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      ougenre: Article
    language: English
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