This study focused on the drug Carbamazepine (CBZ), a very common antiepileptic agent, which is mainly used for tonic-clonic seizures, facial and tongue pain and even bipolar disorder. Despite the cost effectiveness of CBZ, it also brings forward a few areas of concern. CBZ has been shown to produce various clinical responses within patients and unpredictable adverse events such as fatal allergic reactions and liver failure. This downfall occurs in roughly 30-50% of the patients prescribed CBZ. Many patients also develop resistance to CBZ. CBZ concentrations in the patients’ plasma and CNS are associated with the efficacy and toxicity of the drug, which gives rise to the study at hand. This study discussed the screening of patients, before beginning CBZ therapy, for potential markers associated with CBZ efficacy and toxicity.
Carbamazepine is absorbed very slowly in the body and is metabolized mainly by the hepatic genes, CYP3A4 and CYP2C8, to form carbamazepine 10-11 epoxide (CBZ-E). CBZ-E is then metabolized further, by EPHX1, into an inactive form and excreted in urine. The plasma level of CBZ-E, in adults, is about 15-55% of the dose of CBZ given. Carbamazepine also undergoes autoinduction and induces its own metabolism shortly after administration of the drug, leading to decreased plasma levels . Mutations in drug transporter genes, ABCB1 and ABCC2, have also been associated with drug resistant epilepsy and low plasma concentrations of CBZ. In addition, nuclear hormone receptor genes (like NR1I2) are also associated with the transcriptional activation of drug transporters and CYP genes. Due to the many genes associated with the pharmacokinetics (efficacy, bioavailability and toxicity) of CBZ, interpatient ...
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...d and excreted in urine. A mutation in ABCB1 also was linked to high CBZ CL in African-Americans only. The study also associated a variation in NR1I2, causing activation of CYPs and transporters, with CBZ CL and the CBZ-E: CBZ ratio, meaning higher plasma concentrations of CBZ. Although this study did show associations between variations in genetics and pharmacokinetics, future studies must be conducted with a larger sample size to validate the findings. These findings are significant because, in the future epilepsy will be able to be classified by its oligogenic architecture and pharmacogenetic characteristics, providing the appropriate therapy for patients. . This study is extremely important not only for determining genes mutations’ effects for future patient therapy but also in setting the stage future studies to conduct research and have a comparison point.
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