Author/Authors :
HADIDI, ELHAM tehran university of medical sciences tums - Faculty of Pharmacy - Department of Clinical Pharmacy, تهران, ايران , MOJTAHEDZADEH, MOJTABA tehran university of medical sciences tums - Faculty of Pharmacy - Department of Clinical Pharmacy, تهران, ايران , ROUINI, MOHAMMAD REZA tehran university of medical sciences tums - Faculty of Pharmacy - Department of Pharmaceutics, تهران, ايران , EFTEKHAR, BEHZAD tehran university of medical sciences tums - Faculty of Medicine - Sina Hospital,Department of Neurosurgery, تهران, ايران , ABDOLLAHI, MOHAMMAD tehran university of medical sciences tums - Faculty of Pharmacy and Pharmaceutical Sciences Research Center, تهران, ايران , NAJAFI, ATABAK tehran university of medical sciences tums - Faculty of Medicine - Sina Hospital,Department of Anesthesiology, تهران, ايران , KHAJAVI, MOHAMMAD REZA tehran university of medical sciences tums - Faculty of Medicine - Sina Hospital,Department of Anesthesiology, تهران, ايران , REZAEE, SAEED ahvaz jundishapur university of medical sciences - Faculty of Pharmacy - Department of Pharmaceutics, اهواز, ايران , GHAFFARI, REZA tehran university of medical sciences tums - Faculty of Medicine - Sina Hospital, Department of Anesthesiology, تهران, ايران , AFSHAR, MINOO tehran university of medical sciences tums - Faculty of Pharmacy - Department of Pharmaceutics, تهران, ايران
Abstract :
Positive ventilation has shown to have an influence on pharmacokinetic and disposition of some drugs.Beacause phenytoin with a narrow therapautic range, is the most commonly used drug for prophylaxisand treatment of early seizures after acute brain injuries, in the present study the effect of short termPEEP (5-10 cm H2O for at least 8 hours) on phenytoin serum concentration and pharmacokineticparameters such as Vmax and clearance in brain injured patients under mechanical ventilation wasexamined. Ten patients with moderate to severe acute brain injury who were placed on mechanicalventilation with an initial PEEP level of 0-5 cm H2O were included in the study. Patients receivedphenytoin loading dose of 15 mg/kg followed by a maintenance daily dose of 3-7 mg/kg initiated within12 hours of loading dose. Sampels were taken on two different occasions before and after PEEPelevation. Total phenytoin serum concentrations were determined by HPLC method. A time invarientMichaelis-Menten pharmacokinetic model was used to calculate Vmax and clearance for each patient.Derrived variables were calculated as follows: Vmax, 3.5-6.8 and 3.7-8.2 mg/kg/day; Clearance, 0.1-0.7and 0.1-1.2 l/kg/day (before and after PEEP elevation, respectively). Our data have shown a wide rangeof variability (2.6-32.5 mg/l) in phenytoin serum concentrations. There were no statistically significantdifferences in the measured total concentrations (p=0.721) and calculated Vmax and clearance (p=0.285)before and after PEEP elevation. Administration of fluid and inotropic agents, limitation in application ofhigher levels of PEEP and drug interactions, shall be considered as possible explanations for thesefindings.
