How is carbamazepine metabolized?
Carbamazepine is largely metabolized in the liver. CYP3A4 hepatic enzyme is the major enzyme that metabolizes carbamazepine to its active metabolite, carbamazepine-10,11-epoxide 12, which is further metabolized to its trans-diol form by the enzyme epoxide hydrolase.
What is the pharmacokinetics of carbamazepine?
After single oral doses of carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the drug.
How does carbamazepine affect metabolism?
Carbamazepine induces its own metabolism, leading to increased clearance, shortened serum half-life, and progressive decrease in serum levels. Increases in daily dosage are necessary to maintain plasma concentration.
What is the mechanism of action of carbamazepine?
Mechanism of action Carbamazepine is a sodium channel blocker. It binds preferentially to voltage-gated sodium channels in their inactive conformation, which prevents repetitive and sustained firing of an action potential.
How is oxcarbazepine metabolized?
Oxcarbazepine is metabolized by reduction and glucuronidation, resulting in a monohydroxy derivative (MHD). The plasma terminal half-life of oxcarbazepine is between 1 and 2.5 hours, whereas the plasma MHD terminal half-life averages 9.3 ± 1.8 hours after administration of a single dose.
What gene metabolizes carbamazepine?
CBZ is predominantly metabolized by hepatic CYP3A4 and CYP2C8 through formation of carbamazepine 10-11 epoxide (CBZ-E). CBZ-E is an active metabolite equipotent to CBZ [17,18]. CBZ-E is further metabolized by EPHX1 to the inactive carbamazepine-10,11-trans dihydrodiol, (CBZ-diol), which is excreted in the urine.
Does carbamazepine slow metabolism?
Carbamazepine also induces its own metabolism, which means that the length of time it stays in the body for shortens the longer you take the drug. This is called autoinduction and it takes three to five weeks of a fixed dosing regimen before it is complete.
Does Tegretol affect metabolism?
Effect Of Tegretol On Plasma Levels Of Concomitant Agents Tegretol is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6, 2C9/19 and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP 1A2, 2B6, 2C9/19 and 3A4, through induction of their metabolism.
What induces its own metabolism?
Enzyme induction is important in the pathogenesis of hepatotoxicity and therapeutic failure of many drugs. Phenobarbital is a potent enzyme inducer known for hepatotoxicity and for inducing its own metabolism.
Is oxcarbazepine metabolized by the liver?
Metabolism and Excretion Oxcarbazepine is rapidly reduced by cytosolic enzymes in the liver to its 10-monohydroxy metabolite, MHD, which is primarily responsible for the pharmacological effect of Trileptal. MHD is metabolized further by conjugation with glucuronic acid.
How is zonisamide metabolized?
Zonisamide is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering ZONEGRAN to patients with hepatic and renal dysfunction (see CLINICAL PHARMACOLOGY, Special Populations subsection).
Is carbamazepine soluble in water?
Carbamazepine (CBZ) is an antiepileptic drug having poor water solubility and hence poor bioavailability.