Getting a drug like Dilantin into your body is a simple matter, but removing it is far more complex. Dilantin is a prescription anticonvulsant drug used to treat or prevent seizures such as grand mal epilepsy. It is less frequently used to treat irregular heartbeats. Your body needs to metabolize or convert Dilantin into chemical compounds that it can eliminate in your urine. The rate of metabolism varies from person to person due to inherited variations in the makeup of the enzymes that make Dilantin metabolism possible.
Dilantin Liver Metabolism
Very little of the dose of Dilantin you take is eliminated unchanged from your body. Enzymes alter the composition of the Dilantin molecule until it is in a form your kidneys can work with. Most of these enzymes are in the liver and belong to the cytochrome family. Dilantin is metabolized primarily by the enzyme cytochrome p450, but other cytochrome enzymes in the liver and elsewhere are involved as well. Dilantin in the body can rise to a level that overwhelms the ability of enzymes to convert it. Once it reaches this point, the serum levels of Dilantin can rise rapidly to toxic levels.
Dilantin Effects on Metabolism
Dilantin stimulates cytochrome p450 enzyme activity. As a consequence. Dilantin can alter the metabolism of other chemicals. Although your physician usually adjusts your Dilantin dose as needed, you should consider the effect of increased cytochrome p450 activity on other medications you may take. Dilantin decreases the blood serum levels of prescription drugs such as acetaminophen, chloramphenicol, cyclosporine, digoxin, doxycycline, furosemide, intraconazole, meperidine, methadone, oral contraceptives, prednisone and theophylline. If you are taking Dilantin, talk with your physician about possible drug interactions before you take over-the-counter drugs or dietary supplements.
Drugs Affecting Dilantin Metabolism
Variations of the cytochrome p450 enzyme called CYP2C9 and CYP2C19 are responsible for most of the elimination of Dilantin from the body. Drugs that inhibit or increase the activity of these enzymes or interfere with the elimination of Dilantin metabolic products by the kidneys raise or lower your Dilantin serum levels. The drugs diazoxide, primidone, pyridoxine, rifampin and sucralfate reduce Dilantin levels. Drugs that increase Dilantin levels include allopurinol, chlorpheniramine, cimetidine, clarithromycin, fluconazole, fluoxetine, Ibuprofen, ticlopidine, trimethoprim, tolbutamide and valproic acid.
Metabolism Genetics
The rate of Dilantin metabolism and elimination from the body varies by age, sex and ethnic group because there are genetic differences in the functioning of the various enzymes. A 2004 study published in the journal "Therapeutic Drug Monitoring" examined the rate of Dilantin elimination in 169 subjects who were taking the drug for seizure control. The researchers looked at the relationship between dose and ultimate serum Dilantin levels, and they made estimates of the mathematical constants used in the equations that describe the drug's elimination rate. The researchers found that there was considerable variation among the subjects, who were all Taiwanese. They also noted that there was variation between the Taiwanese as a group and other ethnic groups.
References
- PharmGKB: Phenytoin Pathway, Pharmacokinetics
- Dilantin: Dilantin
- Epilepsy Therapy Project: 2006Background for Health Care Provider
- "Therapeutic Drug Monitoring"; Dosage Recommendation of Phenytoin for Patients with Epilepsy with Different CYP2C9/CYP2C19 Polymorphisms; Chin-Chuan Hung, et al.; October 2004
- Inchem: Phenytoin
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