APB Study: Apixaban Pharmacokinetics in Bariatric Patients

Obesity is now the leading health problem of the 21st century. Weight reduction by conservative methods including diet and exercise has had poor success rates. There has been a substantial increase in the use of bariatric surgery to provide sustained weight loss and thus a reduction in the medical comorbidities that are associated with obesity. However, because these procedures may alter the anatomical and physiological aspects of the gastrointestinal system, there is a possibility of altered pharmacokinetics to medications particularly when taken orally. Furthermore, patients typically lose anywhere from 50 to 75% of their estimated excess body mass approximately one to two years following surgery. This successful therapeutic outcome of the surgery may be causing long term changes in the pharmacokinetics that are independent of any direct anatomical or physiologic changes induced by the procedure.

Physicians and surgeons are very interested in oral anticoagulants for this special patient population. To date, there is no approved dosing for the obese patient (especially when considering surgical intervention such as bariatric surgery). VTE is one of the top two causes of morbidity and mortality in the bariatric surgical patient. In the ninth edition of the Antithrombotic Therapy and Prevention of Thrombosis guideline published by the American College of Chest Physicians (1), it is reported that virtually all bariatric surgical patients have at least a moderate risk of VTE, with many patients at high risk. (2) The approach to VTE prophylaxis used by most bariatric surgeons today is a combination of non-invasive and pharmacologic techniques, including sequential compression devices, anti-embolic stockings, anticoagulation, and early ambulation. Traditionally VTE prophylaxis has been accomplished with subcutaneous injection however with the introduction of new oral anticoagulant medications many practitioners are using these anticoagulants without demonstration of effectiveness in this population.

The Johns Hopkins Center for Bariatric Surgery is interested in conducting a pharmacokinetic study of apixaban (an oral anticoagulant with FDA approval for use of VTE prophylaxis and treatment) in the obese adult population to determine if bariatric surgery influences apixaban exposure. More interesting would be to see how the dose may need to change pre- vs. post-bariatric surgery (this will be important for physicians as more and more patients undergo this procedure worldwide and many may require anticoagulation in their future healthcare).

Specific Aim 1: To determine the pharmacokinetics of apixaban in obese patients scheduled to have bariatric surgery with a body mass index (BMI) of 35 kg/m2 or greater.

Hypothesis 1a: Obese patients prior to bariatric surgical intervention, compared to normal weight historical controls, will have a decrease in both Cmax and area under the curve (AUC) when given a single dose of 5 mg of apixaban.