Pharmacokinetics of Simvastatin Post Laparoscopic Sleeve Gastrectomy (LSG)
- Registration Number
- NCT03571802
- Lead Sponsor
- National University Hospital, Singapore
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- Planned for laparoscopic sleeve gastrectomy at National University Hospital
- Taking statin
- Aged 21 or above
- Patient on concomitant treatment with medications/ food/ herbal supplements that may affect the pharmacokinetics of simvastatin: boceprevir, conivaptan, cyclosporine, efavirenz, mitotane, tocilizumab, rifamycin, amiodarone, amlodipine, aprepitant, azithromycin, colchicine, fenofibrate, imatinib, raltegravir, ranolazine, teriflunomide, ticagrelor, fusidic acid, protease inhibitors, telaprevir, telithromycin, gemfibrozil, erythromycin, clarithromycin, carbamazepine, rifampicin, ketoconazole, fluconazole, itraconazole, voriconanzole, diltiazem, verapamil, dexamethasone, prednisolone, phenytoin, ritonavir, indinavir, nelfinavir, bosentan, telithromycin, nefazodone, St John's wort, orlistat, sibutramine and other strong CYP 3A4 inhibitors/ inducers
- Pregnant ladies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description intervention arm Simvastatin simvastatin 20mg once
- Primary Outcome Measures
Name Time Method Area Under Curve (AUC) of simvastatin baseline (before surgery). 3 months after surgery Ratio of AUC of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
Maximum serum concentration (Cmax) of simvastatin baseline (before surgery). 3 months after surgery Ratio of Cmax of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
Time at which maximum serum concentration (Tmax) of simvastatin baseline (before surgery). 3 months after surgery Ratio of Tmax of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
Area Under Curve (AUC) of simvastatin acid baseline (before surgery). 3 months after surgery Ratio of AUC of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
Maximum serum concentration (Cmax) of simvastatin acid baseline (before surgery). 3 months after surgery Ratio of Cmax of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
Time at which maximum serum concentration (Tmax) of simvastatin acid baseline (before surgery). 3 months after surgery Ratio of Tmax of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National University Hospital
🇸🇬Singapore, Singapore