Reference no: EM131731948

Q.1. The best way to effectively administer the drug would be to use an alternative route that would still lower the first pass effect and increase the bioavailability. This would be the parenteral route such as intravenous.What other parenteral methods/routes could you use? However, through genetic engineering, the carrier protein for the drug could still be modified by introducing an amino group that would bypass the mutation and ensure that the drug is delivered into the gastrointestinal tract and absorbed efficiently (Savale 734).Not a general way to bypass mutation, i.e. some specific mutations can be bypassed by an amino group, MOST could not (unless I am missing something--can you provide more details?).

Q. 2. For a patient with a mutation that reduces warfarin metabolism, there is a high chance that giving the same amount of warfarin would increase the warfarin levels in the blood leading to warfarin toxicity. Still,warfarin can be given to this patient safely by reducing the warfarin doses to half and prolonging the intervals between administrations. This can be done by alternating the days of warfarin administration.This is certainly the right idea but how do you come up with the specifics (e.g., 'half,'alternate day therapy)? I would submit you have no way of knowing whether your changes would be enough, too much or too little. How might you find out?

Q.3. Warfarin sensitivity is a pharmacodynamics process.Actually either PK or PD (or both) is(are) possible. What you describe with CYP2C9 is a PK process. It leads to a PD effect. CYP2C9 is an important gene that makes enzymes which play a role in the breakdown of warfarin. Through changes in polymorphism of this gene, its activity is decreased, and this means that warfarin will stay longer in the circulation leading to sensitivity. Again, genetic polymorphisms in VKORC1 gene will reduce the functioning VKORC1 (Dolz?an et al), hence reducing the amount of warfarin needed for inhibition and this is also a pharmacodynamics process leading to warfarin sensitivity. What you describe for VKORC is a typical PD effect. Google VKORC and let me know what you find out.