| OBSERVATION'S |
intended for the quantitative determination of total carbamazepine in serum for therapeutic drug monitoring by fluorescence polarization immunoassay (FPIA). The assay system is for use on the TDx® or the TDxFlxTM (TDx®/TDxFLx®) analyzer. Carbamazepine is an anticonvulsant drug used for the treatment of generalized and partial seizures, and also for the relief of pain associated with trigeminal neuralgia.1-3 It is becoming the anticonvulsant of choice due to its lower incidence of severe side effects. 4,5 Carbamazepine, an iminostilbene derivative chemically related to the tricyclic antidepressants, appears to control seizures by inhibiting excess electrical discharges in the brain. Carbamazepine is routinely administered orally, absorbed slowly and erratically, and once absorbed is rapidly absorbed into all tissues.1 In plasma, about 75% is bound to protein.1, 2 Carbamazepine is metabolized by oxidative liver enzymes to its active 10,11-epoxide metabolite, which may be present at plasma levels 50% those of carbamazepine. The carbamazepine 10,11-epoxide is then metabolized to inactive compounds, mainly the dihydroxide and glucuronides, which are eliminated in the urive.1, 7-9 The ability of carbamazepine to increase its conversion to metabolites, individual variation in the ability to metabolize carbamazepine and a lack of relationship between increases in dose and changes in plasma concentrations make serum level monitoring necessary for individualized dosing of carbamazepine.1, 2, 7, 8, 10 Rall TW, Schleifer LS. Drugs effective in the therapy of the epilepsies. In: The pharmacological basis of therapeutics, Goodman Gilman A. ed. Pergamon Press Inc., New York 1990: 436-461. Barnhart ER. Pub. Physician’s Desk Reference. Oradell, NJ: Medical Economics Co., Inc., 1991: 1015-1019. Killian JM. Tegretol in trigeminal neuralgia with special reference to hematopoietic side effects. Headache 1969; 9: 58-63. Pellock JM. Carbamazepine side effects in children and adults. Epilepsia 1987; 28[suppl 3] : S50-58. Smith DB, Mattson RH, Cramer JA, et. al. Results of a nationwide veterans administration study comparison the efficacy and toxicity of carbamazepine, phenobarbital, phenyton and primidone. Epilepsia 1987; 1987; 28[suppl 3] : S50-58. Kutt G. Carbamazepine. Chemistry and methods of determination. Complex partial seizures and their treatment. In: Penry JK Daly DD, eds. Advances in Neurology. New York, NY: Raven Press, 1975; 11: 249-261. Tomson T, Svenson JO, Hilton-Brown P. Relationship of intraindividual dose to plasma concentration of carbamazepine: indication of dose-dependent metabolism. Therapeutic Drug Monitoring 1989; 11(5): 533-539. Levy RH, Bradley MK. Clinical pharmacokinetics of carbamazepine. J Clin Psychiatry 1988; 49[suppl 4]: 58-61. Eadie MJ. Formation of active metabolites of anticonvulsant drugs. A review of their pharmacokinetic and therapeutic significance. Clin Pharmacokinet 1991; 21(1): 27-41. Privitera MD. Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients. Therapeutic Drug Monitoring 1989; 11: 647-651. |
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