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Acta Medica Iranica، جلد ۶۰، شماره ۱، صفحات ۱۸-۲۵
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عنوان انگلیسی Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury
چکیده انگلیسی مقاله Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.
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نویسندگان مقاله | Seyedeh Sana Khezrnia
Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran


| Bita Shahrami
Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


| Mohammad Reza Rouini
Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


| Atabak Najafi
Department of Anesthesiology and Intensive Care, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran


| Hamid Reza Sharifnia
Department of Anesthesiology and Intensive Care, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran


| Sima Sadrai
Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


| Arezoo Ahmadi
Department of Anesthesiology and Intensive Care, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran


| Aarefeh Jafarzadeh kohneloo
Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran


| Farhad Najmeddin
Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


| Mojtaba Mojtahedzadeh
Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
نشانی اینترنتی https://acta.tums.ac.ir/index.php/acta/article/view/8996
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