NCT03571802

Pharmacokinetics of Simvastatin Post Laparoscopic Sleeve Gastrectomy (LSG)

The Need of Dosing Adjustment for Simvastatin in Obese Patients Post Bariatric Surgery- Laparoscopic Sleeve Gastrectomy (LSG)

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This study aims to investigate the change in systemic exposure of simvastatin post LSG.

Detailed description

Morbid obesity (Body mass index \> 40 kg/m2 or 35-39 kg/m2 with comorbidity; 37.5 kg/m2 for Asians) is a growing global health issue. Bariatric surgery is the only intervention that has demonstrated sustainable reduction in weight and comorbidities.1,2 Among the various bariatric procedures, laparoscopic sleeve gastrectomy (LSG) has rapidly gained popularity worldwide.3,4 Physiological alterations following LSG include reduction in gastrointestinal surface and reduced retention of food. Bioavailability of drugs may be affected but published literature in this area is sparse and studies are usually small and uncontrolled.5-7 Moreover, some reports concerning gastric banding and jejunoileal bypass are no longer practiced because of the associated risk. In general, bioavailability of orally administered drug changes with a reduction in gastrointestinal area. While Kroll et al showed slight increase in area under curve of rivaroxaban post bariatric surgery8, Skottheim et al demonstrated significant but variable change in systemic exposure of atorvastatin after gastric bypass (from threefold decrease to twofold increase) that diminished but was sustained with time (21-45 months post gastric bypass)9-10. No study has investigated the change in pharmacokinetics of simvastatin post LSG. Simvastatin is a widely-used lipid-lowering agent with a low bioavailability of 5% due to the extensive first pass metabolism.11 As simvastatin undergoes hydrolysis in the stomach to the active form12, it is postulated that bioavailability of simvastatin will decrease after LSG.13-15 A decrease in bioavailability may be associated with reduced efficacy. Authors of review articles suggested choosing an alternative agent to simvastatin post bariatric surgery. However, such recommendation is largely based on theoretical concern rather than solid evidence.14,15 A previous study attempted to model the pharmacokinetics of simvastatin post Roux-en-Y and biliopancreatic diversion with duodenal switch.13 The data is not applicable to LSG and the model did not take into account of the pH-dependent hydrolysis. This will be the first study aiming to investigate the change in systemic exposure of simvastatin post LSG.

Conditions

• Obesity
• Hyperlipidemias

Interventions

Type	Name	Description
DRUG	Simvastatin	* The subject will take simvastatin 20mg at 0 h (after stopping simvastatin for 5 days). 5 mL of blood will be sampled at 0 h, 1 h, 2 h, 3 h, 5 h, 7 h. * There will be 2 blood sampling sessions: 1 before and the other 3 months after surgery.

Timeline

• Start date: 2018-06-13
• Primary completion: 2025-06-30
• Completion: 2025-06-30
• First posted: 2018-06-28
• Last updated: 2022-04-08

Locations

1 site across 1 country: Singapore

Regulatory

• FDA-regulated drug study