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The Complexity of Bariatric Patient's Pharmacotherapy: Sildenafil Biopharmaceutics and Pharmacokinetics before vs. after Gastric Sleeve/Bypass.

Authors :
Porat, Daniel
Dukhno, Oleg
Cvijić, Sandra
Dahan, Arik
Source :
Pharmaceutics. Dec2023, Vol. 15 Issue 12, p2795. 13p.
Publication Year :
2023

Abstract

Postbariatric altered gastrointestinal (GI) anatomy/physiology may significantly harm oral drug absorption and overall bioavailability. In this work, sildenafil, the first phosphodiesterase-5 (PDE5) inhibitor, was investigated for impaired postbariatric solubility/dissolution and absorption; this research question is of particular relevance since erectile dysfunction (ED) is associated with higher body mass index (BMI). Sildenafil solubility was determined both in vitro and ex vivo, using pre- vs. postsurgery gastric contents aspirated from patients. Dissolution tests were done in conditions mimicking the stomach before surgery, after sleeve gastrectomy (post-SG, pH 5), and after one anastomosis gastric bypass (post-OAGB, pH 7). Finally, these data were included in physiologically based pharmacokinetic (PBPK) modelling (GastroPlus®) to simulate sildenafil PK before vs. after surgery. pH-dependent solubility was demonstrated with low solubility (0.3 mg/mL) at pH 7 vs. high solubility at pH 1–5, which was also confirmed ex vivo with much lower solubility values in postbariatric gastric samples. Hampered dissolution of all sildenafil doses was obtained under post-OAGB conditions compared with complete (100%) dissolution under both presurgery and post-SG conditions. PBPK simulations revealed delayed sildenafil absorption in postbariatric patients (increased tmax) and reduced Cmax, especially in post-OAGB patients, relative to a presurgery state. Hence, the effect of bariatric surgery on sildenafil PK is unpredictable and may depend on the specific bariatric procedure. This mechanistically based analysis suggests a potentially undesirable delayed onset of action of sildenafil following gastric bypass surgery. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19994923
Volume :
15
Issue :
12
Database :
Academic Search Index
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
174463655
Full Text :
https://doi.org/10.3390/pharmaceutics15122795