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Timing of maintenance phenytoin therapy after intravenous loading dose
J J Riviello1, E J Roe, J I Sapin
1Department of Pediatrics, Temple University School of Medicine, Philadelphia, Pennsylvania.
Insights
Determining the right time for maintenance phenytoin therapy is crucial for seizure control in children. This study found that the 2-hour phenytoin level effectively predicts therapeutic drug concentrations, guiding timely dosing adjustments.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
Background:
- The optimal timing for initiating maintenance phenytoin therapy in pediatric patients remains unestablished.
- Maintaining therapeutic phenytoin levels is essential for effective seizure management.
Purpose of the Study:
- To establish a protocol for determining the appropriate timing of maintenance phenytoin therapy in children.
- To analyze serial phenytoin levels and identify predictors of therapeutic drug concentrations.
Main Methods:
- A protocol involving an 18 mg/kg phenytoin loading dose and serial level monitoring at 2, 6, and 12 hours was implemented in 20 pediatric patients.
- Patients were categorized into therapeutic and subtherapeutic groups based on 12-hour phenytoin levels.
- Statistical analysis compared 2-hour levels and plasma concentration decline rates between groups.
Main Results:
- All patients achieved therapeutic phenytoin levels (>10 µg/mL) at 2 hours post-loading dose.
- Therapeutic levels were maintained at 6 hours in 16/20 patients and at 12 hours in 10/20 patients.
- Significantly higher mean 2-hour levels (22.7 vs. 15.6 µg/mL) and slower concentration decline rates (0.7 vs. 1.02 µg/mL/hr) were observed in the therapeutic group.
Conclusions:
- The 2-hour post-loading dose phenytoin level serves as a reliable indicator for guiding the timing of maintenance therapy.
- A predictive equation was developed to estimate the duration of the therapeutic phenytoin range.
- This approach allows for individualized adjustments to phenytoin dosing schedules to ensure sustained therapeutic levels.
Abstract:
The specific timing of maintenance phenytoin therapy in children has not been addressed. Prevention of a subtherapeutic phenytoin level is important for seizure control. We devised a protocol using an 18 mg/kg loading dose of phenytoin with serial levels (obtained after 2,6,12 hours) and analyzed the results in 20 consecutive patients. A therapeutic level (greater than 10 micrograms/ml) was present in all patients at 2 hours, in 16 of 20 at 6 hours, and in 10 of 20 at 12 hours. The patients were divided into 2 groups by the 12-hour levels: group I: therapeutic level; and group II: subtherapeutic level. The mean 2-hour level in group I was 22.7 micrograms/ml versus 15.6 micrograms/ml in group II (P less than 0.001). The mean decline in plasma concentration in individual patients was 0.7 micrograms/ml/hr in group I versus 1.02 micrograms/ml/hr in group II (P less than 0.05). We now use the 2-hour level to decide the timing of maintenance phenytoin therapy and have devised an equation to estimate the duration of the therapeutic range. Phenytoin can be administered at 12 hours when the 2-hour level is satisfactory or earlier when the 2-hour level indicates that a subtherapeutic level will occur.