{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:39:22Z","timestamp":1785523162290,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u00ae) 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\u20135, 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics15122795","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:41:35Z","timestamp":1702878095000},"page":"2795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Complexity of Bariatric Patient\u2019s Pharmacotherapy: Sildenafil Biopharmaceutics and Pharmacokinetics before vs. after Gastric Sleeve\/Bypass"],"prefix":"10.3390","volume":"15","author":[{"given":"Daniel","family":"Porat","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-4237","authenticated-orcid":false,"given":"Oleg","family":"Dukhno","sequence":"additional","affiliation":[{"name":"Department of Surgery B, Soroka University Medical Center, Beer-Sheva 8410101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-791X","authenticated-orcid":false,"given":"Sandra","family":"Cviji\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3498-3514","authenticated-orcid":false,"given":"Arik","family":"Dahan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1016\/j.juro.2009.07.089","article-title":"Diabetes, obesity and erectile dysfunction: Field overview and research priorities","volume":"182","author":"Chitaley","year":"2009","journal-title":"J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13282","DOI":"10.1111\/and.13282","article-title":"Visceral adiposity index is useful for evaluating obesity effect on erectile dysfunction","volume":"51","author":"Akdemir","year":"2019","journal-title":"Andrologia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Minambres, I., Sarda, H., Urgell, E., Genua, I., Ramos, A., Fernandez-Ananin, S., Balague, C., Sanchez-Quesada, J.L., Bassas, L., and Perez, A. (2022). 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