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[Bio-availability of phenytoin free-acid serum level determinations whilst using a lactose-based tablet-preparation
Insights
Phenytoin dosage in children requires careful consideration of the specific drug formulation. Different phenytoin preparations and excipients significantly impact bioavailability, affecting therapeutic serum levels and intoxication risk.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Pediatric Neurology
Context:
- Assessing phenytoin serum levels in pediatric patients is crucial for effective epilepsy management.
- Many children receive combination antiepileptic drug therapy, complicating dosage individualization.
- Outpatient treatment is common, necessitating reliable and predictable drug efficacy.
Purpose:
- To determine therapeutic phenytoin serum levels in children receiving steady-state therapy.
- To investigate the relationship between oral phenytoin dosage, serum levels, and clinical signs of intoxication.
- To evaluate the influence of drug formulation and excipients on phenytoin bioavailability.
Summary:
- Phenytoin serum levels were measured in 103 children using radio-immunoassay.
- A therapeutic range of 10-20 mcg/ml was achieved with approximately 6.1 mg/kg/day.
- Higher doses (7.1 mg/kg/day) led to elevated levels (>20 mcg/ml) and intoxication signs in 27 children.
- Drug bioavailability depends on the phenytoin salt/acid form and tablet excipients, making general recommendations unreliable.
Impact:
- Highlights the critical role of specific phenytoin formulations and excipients in achieving therapeutic outcomes.
- Underscores the danger of generalized dosing guidelines for phenytoin in pediatric epilepsy.
- Emphasizes the need for individualized dosing and formulation-specific considerations in clinical practice.
Abstract:
Phenytoin serum levels were determined in 103 children during the steady state of phenytoin therapy using a radio-immuno-assay. 94% of the patients had been treated as outpatients, 54% received phenytoin in combination with other antiepileptic drugs. The preparation used was phenytoin as free acid in lactose tablets (Epilan D). A therapeutic serum level of 10-20 mcg/ml was reached by an oral intake of 6,1 +/- 1,6 mg/kg/d. 27 children had plasma levels above 20 mcg/ml, their oral dose was 7,1 +/- 1,8 mg/kg/d. Most of these children showed clinical signs of intoxication. The bioavailability of phenytoin preparations is not only depended on the type of the substance used (salt, free acid), but also on the excipients used for the preparation of tablets. Therefore, general dosage recommendations are useless and even dangerous, unless the preparations used are extensively specified.