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Iranian Journal of Basic Medical Sciences، جلد ۲۵، شماره ۷، صفحات ۸۶۵-۸۷۰
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عنوان انگلیسی Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats
چکیده انگلیسی مقاله Objective(s): Diabetes mellitus (DM) affects the pharmacokinetics of drugs. Ranolazine is an antianginal drug that is prescribed in DM patients with angina. We decided to evaluate the effect of DM on the pharmacokinetics of ranolazine and its major metabolite CVT-2738 in rats.Materials and Methods: Male rats were divided into two groups: DM (induced by 55 mg/kg Streptozotocin (STZ)) and non-DM. All animals were treated with 80 mg/kg of ranolazine for 7 continuous days. The blood samples were collected immediately at 0 (prior to dosing), 1, 2, 3, 4, 8, and 12 hr after administration of the 7th dose of ranolazine. Serum ranolazine and CVT-2738 concentrations were determined using the high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were calculated using a non-compartmental model and compared between the two groups.Results: The peak serum concentration (Cmax) and area under the curve (AUC) of ranolazine significantly decreased in DM compared with non-DM rats. DM rats showed significantly higher volumes of distribution (Vd) and clearance (CL) of ranolazine than non-DM rats. DM did not affect Ke, Tmax, and T1/2 of ranolazine. The concentration of metabolite was lower than the HPLC limit of detection (LOD).Conclusion: It was found that streptozotocin-induced DM increased Vd and CL of ranolazine, thereby decreasing the AUC of the drug. Therefore, dosage adjustment may be necessary for DM patients, which requires further clinical studies.
کلیدواژه‌های انگلیسی مقاله Clearance, Diabetes Mellitus, Pharmacokinetics, Ranolazine, Volume of distribution
نویسندگان مقاله | Habibeh Mashayekhi-sardoo
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


| Hossein Kamali
Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran|Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


| Soghra Mehri
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


| Amirhossein Sahebkar
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran|Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran|Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


| Mohsen Imenshahidi
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran|Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran


| Amir Hooshang Mohammadpour
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran|Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
نشانی اینترنتی https://ijbms.mums.ac.ir/article_20646.html
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