ADMET-Absorption, Distribution, Metabolism, Excretion, and Toxicity

StatusFDA approved
AdministrationN/A
PharmacologyAn anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, and post-traumatic stress disorder.

Absorption_value100.0
Absorption (description)Slowly but almost completely absorbed after oral administration.
Caco_2N/A
Bioavailability70.0

MetabollsmMetabolic reactions, catalysed by cytochrome isoenzymes CYP3A4 and CYP2C8, include epoxidation to form the 10,11-epoxide, which is active, followed by hydroxylation to trans-10,11-dihydro-10,11-dihydroxycarbamazepine; glucuronic acid conjugation also occurs. The rate of metabolism is higher in children than in adults and levels of the epoxide may be higher in children than in adults.
Half life18~65 h (mean 35) after single doses; reduced during chronic treatment to about 10~30 h for adults and 8~19 h for children

ExcretionAbout 25% of a dose is excreted in the urine as the dihydroxy metabolite, together with 2% as the 10,11-epoxide and less than 10% as unchanged drug; other metabolites identified in the urine include carbamazepine-N-glucuronide, iminostilbene, and several monohydroxy- and trihydroxycarbamazepine isomers. About 30% of a dose is eliminated in the faeces. Carbamazepine crosses the placental barrier and is distributed into breast milk.
Urinary Excretion<1
Clerance13 ml/min/kg.

ToxicityThe estimated minimum lethal dose is 5 g. Plasma concentrations of 2.4 to 6.0 to 10.5 mg/L have been associated with slight toxic effects and concentrations of 3.2 to 10 to 21 mg/L with severe toxicity. A 15-year-old girl was admitted having taken at least 23 tablets of Tegretol (4.6 g) 6 h earlier. The carbamazepine level was 44.8 mg/L. Orogastric lavage was followed by activated charcoal. Within 20 h of admission there was no improvement in her neurological status, so it was decided to perform plasmapheresis. The carbamazepine level immediately after the procedure was 23.9 mg/L, and at the 36th, 60th and 84th hours was 72, 33 and 4.7 mg/L, respectively. The patient was discharged on the 4th day. [A. Duzova et al.,Hum. Exp. Toxicol.,2001, 20, 175–177.]
LD50 (rat)N/A
LD50 (mouse)N/A