Evaluation of phenytoin utilization based on key pharmacokinetic parameters in patients with head trauma

ABSTRACT

Phenytoin is commonly administered as an anticonvulsant agent to critically traumatic patients for seizure prophylaxis and treatment. It exhibits non-linear pharmacokinetic characteristic and requires frequent plasma level monitoring and dose adjustment. Based on the previous study, it is often difficult to achieve therapeutic levels in patients with head trauma using the recommended phenytoin dosing strategies. Therefore, we conducted a prospective, randomized study to evaluate pharmacokinetic parameters of phenytoin in patients with head trauma. In this prospective randomized study, eighty-three patients were enrolled. The dosing regimen of phenytoin was designed and individualized for each patient based on available population pharmacokinetic data and was compared with the administered dose. The peak and trough concentrations of collected blood samples were determined by TDX. Statistical analysis of the findings indicated that there were significant differences between administered doses of phenytoin and calculated doses based on peak and trough [P<0.0001]. Additonally, our findings indicate the significant difference between previous population Vmax and Vmax obtained from this study. Furthermore, this study showed that phenytoin plasma concentrations were sub therapeutic in the majority of cases [71%].It seems that blood level monitoring ot phenytoin in patients with neurosurgical trauma on the basis of drug pharmacokinetic parameters such as Vmax is necessary