Effect of Laparoscopic Sleeve Gastrectomy on the Pharmacokinetics of Oral Omeprazole Using a Population Approach

Abstract

Omeprazole is commonly prescribed to obese patients and patients after laparoscopic sleeve gastrectomy (LSG). The pharmacokinetics of oral omeprazole after LSG are still unknown. Therefore, the aim of this study was to investigate the pharmacokinetics of oral omeprazole in obese patients before and after LSG. A total of 331 blood samples were collected from 62 obese patients preoperatively (visit 1) followed by 41 patients 7 days post-LSG (visit 2) and 20 patients 1 month post-LSG (visit 3). Population pharmacokinetic analysis was performed using NONMEM to characterize the effect of LSG on omeprazole absorption and disposition. A one-compartment model with 12 transit absorption compartments and linear elimination successfully described the data. Compared with pre-surgery, the oral omeprazole time to maximum plasma concentration (Tmax) was reduced and maximum plasma concentration (Cmax) was higher, but the apparent clearance (CL/F) and area under the plasma concentration–time curve (AUC) were unchanged 7 days and 1 month after surgery. In addition, the CYP2C19 genotype and liver function exhibited a significant influence on omeprazole CL/F. LSG increased the rate of omeprazole absorption but did not affect omeprazole exposure. A dose of 20 mg omeprazole once daily may be adequate for relieving gastrointestinal tract discomfort at short-term follow-up post-LSG.