Pharmacokinetics Factors Relating to the Therapeutic Use of Phenytoin Resulting in Toxicity of the Drug Accumulating with Multiple Dosing

Pharmacokinetics Factors Relating to the Therapeutic Use of Phenytoin Resulting in Toxicity of the Drug Accumulating with Multiple Dosing

  • Submitted By: ryzoh
  • Date Submitted: 07/07/2010 2:50 PM
  • Category: Science
  • Words: 347
  • Page: 2
  • Views: 301

Phenytoin is an anticonvulsant medicine that is taken for partial seizures in epilepsy amongst other things. It works by prolonging the inactivation state of sodium-ion channels, therefore reducing the ability of neurons to fire at high frequencies. its formulations include tablets, capsules, oral suspensions and intravenous forms.

Careful monitoring is required when treating patients with phenytoin because it has a very narrow therapeutic range, and anything outside of the therapeutic range leads to toxicity or inaffectiveness. The relationship between dose and plasma concentration is non linear. Also, when dealing with anti-epileptic medications, it is to be noted that there are many drug interactions and complications involving pharmacokinetics.

A safe dosage for phenytoin is taking one tablet twice daily in which a loading dose is required because of the narrow therapeutic range and high toxicity rate, the therapeutic range must be met. The dosage is then lowered to keep within the therapeutic range.

In order to achieve therapeutic ranges of phenytoin in plasma concentration 10-20 mcg/ml is suggested. However, toxicity can occur in individuals in multiple dosing regimens. This is highlighted in the elderly as they have slower metabolisms and are prone to renal/hepatic impairment, leading to toxicity when treated with phenytoin. this is because phenytoin clearance is lowered, meaning there is a higher level of it in the plasma. In infants or young adults, the metabolism is quicker than adults and therefore the clearance is higher and they require more frequent doses of phenytoin and that can increase risk of toxicity or the seizures may continue because of lack of efficacy.

Drug interactions are also a large contributor to toxicity of phenytoin. The interactions are brought on by hepatic enzyme induction and/or hepatic enzyme inhibition. Drugs such as Carbamazapine increases the plasma concentration of phenytoin making it toxic to the plasma....

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