Hyperlipidemias, Obesity
Conditions
Keywords
pharmacokinetics, simvastatin, bariatric surgery, laparoscopic sleeve gastrectomy
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.
Interventions
DRUGSimvastatin
* 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.
Sponsors
National University Hospital, Singapore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pharmacokinetic parameters of simvastatin before and after laparoscopic sleeve gastrectomy will be compared in 10 patients. Each patient will serve as their own control for comparison.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Planned for laparoscopic sleeve gastrectomy at National University Hospital * Taking statin * Aged 21 or above
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Singapore
Contacts
Primary ContactAsim Shabbir, MBBS
Backup ContactElaine Lo, PharmD
Outcome results
None listed