General questions 7 : Carbamazepine

General question number seven Carbamazepine and antiepileptic is greater than 99% metabolized to a metabolite which is at 10, 11 epoxide the metabolite has little antiepileptic effect but does cause idiosyncratic adverse reaction so if the drug is given to a patient with GFR of 50 and numbers have compromised of 50% compromised What is your recommendation for the patients dosing regimen? Let’s look through the answers. First the dose should be decreased compared to the standard regimen Well the drug is so extensively metabolized and therefore we really don’t have to worry too much about the dose So A is pretty much out. B the dose should be increased compared to the standard regimen. This is to the opposite.

No drug should be increased because of because of a compromised renal function and D the drug is contraindicated for a patient with renal insufficiency. This is not the case. And the most likely this type of answer is red herring also. That is a distractor. So let’s look at choice number three. C so standard dose regimen is appropriate for this patient simply because carbamazepine is greater than 99% metabolize since liver is doing a job so in renal failure, we don’t have to worry too much about dosing regimen. Again some PK information is helpful for you to make the right choice.

We know carbamazepine is 70% absorbed it is 99% metabolized and that the 10, 11 epoxide is further metabolized in the liver and excreted by the kidneys. So in patient was the liver function and liver dysfunction in fact the carbamazepine dosage need to be adjusted not in renal failure but in liver dysfunction. Because the epoxide metabolite may accumulated and this epoxide metabolic causes teratogenic toxicity protein binding is 75% and that we have kinetic information and clearance on volume distribution and on half-life