Pharmacokinetic Profiles of Lansoprazole in Patients With Morbid Obesity Post‐Roux‐en‐Y Gastric Bypass Surgery

ABSTRACT Data on the effects of Roux‐en‐Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post‐surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre‐ and post‐surgery, using a validated high‐performance liquid chromatography technique. CYP2C19 genotyping classified participants as normal metabolizers (*1/*1) or intermediate metabolizers (*1/*2 and *1/*3). Pharmacokinetic parameters, including the area under the plasma concentration‐time curve from 0 to 8 h (AUC0–8 h), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m2) were enrolled. Post‐surgery, AUC0–8 h and Cmax decreased by 16% (p = 0.009) and 31% (p = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (p = 0.007) was observed in CYP2C19 normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in CYP2C19 normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post‐RYGB patients. Trial Registration: ClinicalTrials.gov identifier: TCTR20220118001