Do total concentrations of phenytoin predict free concentrations in Malaysian pediatric patients?

摘要

Phenytoin is the highly protein-bound drug. Its free fraction represents the pharmacologically active portion of administered medication. This study is to determine the relationship between estimated free concentrations and measured total phenytoin concentrations, and to estimate phenytoin pharmacokinetic parameters (V maxand K m). There were 52 steady-state phenytoin concentrations from 52 pediatric patients with hypoalbuminemia. Sheiner-Tozers equation was used to estimate free concentration (C fest) of phenytoin. of 52 stead y state to tal phenytoin concentrations, 11.5%, 25%, 63.5% were found toxic, therapeutic and subtherapeutic respectively, of 52 free concentrations, 21.2%, 28.8%, 50% were found toxic, therapeutic and subtherapeutic respectively. 5 patients (9.7%) had toxic free levels (>2 g/ml) when si multaneously measured total levels were therapeutic (<20 g/ml). The Mean ± SD for K mand V maxin 47 patients were 4.495 ± 3.508 mg/L and 9.049 ± 5.357 mg/kg/day but the mean o f K mand V max for those 5 patients were 6.18±1.749 mg/L and 5.352 ± 2.085 mg/kg/day. There was a correlation between free concentratio n and total concentrations (r2= 0.83). The authors observed that there was correlation between free and total phenytoin concentrations even with an increased variability in protein binding observed in patients. Free phenytoi n concentration estimation and monitoring requires further investigat ion