Fosphenytoin Half-Life
The conversion half-life of fosphenytoin to phenytoin is approximately 15 minutes, after which fosphenytoin is completely metabolized to its active form, phenytoin. 1
Conversion Pharmacokinetics
Fosphenytoin itself has a conversion half-life of 8-15 minutes when administered intravenously, during which it is rapidly converted to phenytoin by blood and tissue phosphatases 2, 3, 4, 5
The FDA label specifically states the conversion half-life is approximately 15 minutes 1
Following IV administration, maximum plasma fosphenytoin concentrations are achieved at the end of infusion, with complete conversion to phenytoin occurring rapidly thereafter 1
Route-Specific Considerations
Intravenous Administration
- Therapeutic free phenytoin concentrations are achieved within minutes after completion of the infusion 1, 2
- The rapid 15-minute conversion allows fosphenytoin infused at 100-150 mg PE/min to produce phenytoin levels comparable to phenytoin sodium infused at 50 mg/min 1
Intramuscular Administration
- Following IM administration, the absorption rate becomes the rate-limiting step with a half-life range of 22-41 minutes 3
- Peak fosphenytoin concentrations occur at approximately 30 minutes post-dose 1
- Peak phenytoin concentrations occur at 2-4 hours after IM administration 2
- Therapeutic phenytoin levels are generally achieved within 30 minutes to 1 hour after IM injection 1, 2
Clinical Implications
Fosphenytoin is entirely eliminated through metabolism to phenytoin—it is not excreted unchanged in urine 1
The bioavailability of derived phenytoin is approximately 100% following either IV or IM administration 1, 2, 3
Once converted to phenytoin, the subsequent elimination follows phenytoin pharmacokinetics (half-life 11-55 hours in children, 63-88 hours in neonates) 6