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Drug interaction between phenytoin and allopurinol
Journal of Pharmacobio-Dynamics
|January 1, 1990
Summary
Repeated high doses of allopurinol significantly slow phenytoin elimination and reduce its metabolite excretion. This drug interaction is not due to effects on liver metabolism or kidney function.
Area of Science:
- Pharmacology
- Drug Metabolism
- Toxicology
Background:
- Phenytoin (DPH) and allopurinol are used together for neurological conditions.
- The interaction mechanism between DPH and allopurinol remains poorly understood.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between phenytoin and allopurinol.
- To elucidate the mechanism underlying the observed drug interaction.
Main Methods:
- Repeated and single-dose administration of allopurinol in animal models.
- Measurement of phenytoin and its metabolite p-hydroxyphenytoin (HPPH) levels.
- Assessment of hepatic extraction and renal plasma flow.
- In vitro studies on DPH hydroxylation and enzyme activity.
Main Results:
- Repeated high-dose allopurinol significantly reduced DPH elimination and HPPH excretion.
- Single-dose allopurinol did not affect DPH pharmacokinetics.
- Allopurinol did not alter hepatic DPH extraction or renal plasma flow.
- In vitro studies showed minimal inhibition of DPH hydroxylation, inconsistent with in vivo findings.
Conclusions:
- Repeated allopurinol administration interferes with phenytoin metabolism.
- The interaction is not mediated by cytochrome P-450 dependent monooxygenase reactions.
- Further research is needed to clarify the exact mechanism of this drug interaction.