| OBSERVATION'S |
Phenytoin is an anticonvulsant drug used to treat all forms of epilepsy except absence seizures. Phenytoin acts directly on the central nervous system to block seizure activity.1-3 Phenytoin absorption following oral dosing is variable.2,3 Peak plasma concentrations may occur from as early as three hours to as late as twelve hours following drug administration.2 Once absorbed, phenytoin is rapidly distributed into all tissues. The half-life of phenytoin ranges from 20 to 60 hours at therapeutic concentrations. Phenytoin is bound extensively (about 90%0 to plasma proteins, mainly albumin.2 Metabolism of phenytoin occurs primarily in the liver. The major metabolite, the parahydroxyphenyl derivative, is apparently inactive.2-5 Phenytoin exhibits dose-dependent metabolism and at higher serum concentrations small dosage changes can result in large serum concentration changes. Approximately 2-5% of the drug is excreted unchanged in the urine.2 In addition, concomitant medications may increase or decrease serum phenytoin levels.2,3,6 Monitoring serum phenytoin concentrations is recommended to guide dosage and avoid toxicity effects due to patient differences in the absorption, metabolism and clearance of phenytoin.2,3,6,7 Immunoassays for phenytoin using a fluorescence polarization immunoassay have been described.8,9 Pippenger CE. Effective seizure control requires drug monitoring. In: Battaglia DJ ed. Clinical Chemistry new special section. Washington DC: American Association of Clinical Chemistry 1980: S1-10. Rall TW, Schleifer LS. Drugs effective in the therapy of epilepsies. In: The pharmacological basis of therapeutics, Goodman Gilman A, et. al., ed. Pergamon Press Inc., New York 10523 1990: 436-461. Barnhart ER. Pub. Physician’s Desk Reference. Oradell, NJ: Medical Economics Co., Inc., 1991: 1640-1642. Glazko AJ. Early adventures in drug metabolism: 4.diphenylhydantoin (phytoin). Therapeutic Drug Monitoring 1987; 9:407-415. Eadie MJ. Formation of active metabolites of anticonvulsant drugs. A review of their pharmacokinetic and therapeutic signivicance. 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. Ther Drug Monitor 1989; 11: 647-651. Levine M, Chang T. Therapeutic drug monitoring of phenytoin. Rationale and current status. Clin Pharmacokinet 1990; 19(5): 341-358. Lu-Steffes M, Jolley ME, Pittluck G, et al. Fluorescence polarization immunoassays of phenytoin and phenobarbital. ClinChem 1981; 27: 1093. McGregor AR, Crookall-Greening JO, Landon J, Smith DS. Polarization fluorimmunoassays of phenytoin. Clin Chem Acta; 1978; 83: 161-166. |
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