JP234 is a novel, oral antiarrhythmic agent for controlling heart rate in chronic atrial fibrillation. In clinical trials it has been tolerated well and there are no contraindications to its use. It is effective in doses of 50, 75 or 100 mg once daily, some patients requiring the 100 mg dose. JP234 is metabolised in the liver and has a half-life of about 24 hours. In vitro studies suggest that it is likely to cause induction of CYP3A4 and CYP2C9. It is recommended that patients with chronic atrial fibrillation should be anticoagulated to prevent thromboembolism and most patients who will receive JP234 will also be taking warfarin, which is partly metabolised by these cytochrome enzymes.
Part 1—1500 words
Design a study to investigate the potential of JP234 to induce the metabolism of a single dose of warfarin. Your design must include details of:
• Study design
• Your choice of population of study subjects and particular inclusion and exclusion criteria
• Dose and schedule of dosing of JP234
• Dose of warfarin
• Schedule for blood sampling
• Assays you will require
• Endpoints and Analysis of Results
Part 2 –700 words
If JP234 causes clinically important enzyme induction at relevant doses, a possible recommendation would be for patients to switch from warfarin to Rivaroxaban one of the new oral anticoagulants that act by inhibiting Factor Xa. Discuss briefly whether this recommendation is likely to be advantageous
Sample Solution