Pharmacokinetic Behavior of Phenytoin in Head Trauma and Cerebrovascular Accident Patients in an Iranian Population

Shahnaz Alimardani; Sima Sadrai; Hamidreza Taghvaye Masoumi; Pooneh Salari; Atabak Najafi; Behzad Eftekhar; Mojtaba Mojtahedzadeh

doi:10.4103/jrpp.JRPP_17_58

Pharmacokinetic Behavior of Phenytoin in Head Trauma and Cerebrovascular Accident Patients in an Iranian Population

J Res Pharm Pract. 2017 Oct-Dec;6(4):217-222. doi: 10.4103/jrpp.JRPP_17_58.

Authors

Shahnaz Alimardani¹, Sima Sadrai², Hamidreza Taghvaye Masoumi¹, Pooneh Salari³, Atabak Najafi⁴, Behzad Eftekhar⁵, Mojtaba Mojtahedzadeh¹

Affiliations

¹ Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran.
³ Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Anesthesiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Neurosurgery, Nepean Hospital, the University of Sydney, Sydney, Australia.

Abstract

Objective: Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI).

Methods: This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA).

Findings: The V_maxand K_mwere significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (C_p) and the C_p/dose ratio were significantly higher in the CVA group patients during the first sampling (P < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients (P < 0.05). In addition, no significant correlation was observed between V_max, K_m, C_p, C_p/dose ratio, and APACHE II scores at the time of sampling.

Conclusion: Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient's outcome after a severe HT.

Keywords: Brain injury; Iranian population; Phenytoin; pharmacokinetic.