Influence of Bariatric Surgery on Levetiracetam Clinical Effectiveness: Case Series

Margolin, Nadia; Porat, Daniel; Dahan, Arik; Lavon, Ophir

doi:10.1007/s11695-022-06135-4

Cited by 4 publications

(1 citation statement)

References 5 publications

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“…Other mechanisms involved in the pharmacokinetics of these drugs may also be affected by bariatric surgery [ 64 , 65 , 66 , 67 , 68 ]. For example, the activity of CYP3A enzymes is increased with weight loss [ 69 , 70 , 71 ], and since sildenafil is mainly metabolized by CYP3A4, its postbariatric plasma levels may be further decreased.…”

Section: Discussionmentioning

confidence: 99%

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

Porat,

Dukhno,

Cvijić

et al. 2023

Pharmaceutics

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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.

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