Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats
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:...
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| Format: | Article |
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Mashhad University of Medical Sciences
2022-07-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_20646_6b6322fe9f40ebe8877e67759568761c.pdf |
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| author | Habibeh Mashayekhi-sardoo Hossein Kamali Soghra Mehri Amirhossein Sahebkar Mohsen Imenshahidi Amir Hooshang Mohammadpour |
| author_facet | Habibeh Mashayekhi-sardoo Hossein Kamali Soghra Mehri Amirhossein Sahebkar Mohsen Imenshahidi Amir Hooshang Mohammadpour |
| author_sort | Habibeh Mashayekhi-sardoo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T15:17:24Z |
| format | Article |
| id | doaj.art-52961dd5d7a44a8d8d59843023886361 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-04-12T15:17:24Z |
| publishDate | 2022-07-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-52961dd5d7a44a8d8d598430238863612022-12-22T03:27:34ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-07-0125786587010.22038/ijbms.2022.64391.1415620646Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic ratsHabibeh Mashayekhi-sardoo0Hossein Kamali1Soghra Mehri2Amirhossein Sahebkar3Mohsen Imenshahidi4Amir Hooshang Mohammadpour5Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranObjective(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.https://ijbms.mums.ac.ir/article_20646_6b6322fe9f40ebe8877e67759568761c.pdfclearancediabetes mellituspharmacokineticsranolazinevolume of distribution |
| spellingShingle | Habibeh Mashayekhi-sardoo Hossein Kamali Soghra Mehri Amirhossein Sahebkar Mohsen Imenshahidi Amir Hooshang Mohammadpour Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats Iranian Journal of Basic Medical Sciences clearance diabetes mellitus pharmacokinetics ranolazine volume of distribution |
| title | Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats |
| title_full | Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats |
| title_fullStr | Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats |
| title_full_unstemmed | Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats |
| title_short | Comparison of pharmacokinetic parameters of ranolazine between diabetic and non-diabetic rats |
| title_sort | comparison of pharmacokinetic parameters of ranolazine between diabetic and non diabetic rats |
| topic | clearance diabetes mellitus pharmacokinetics ranolazine volume of distribution |
| url | https://ijbms.mums.ac.ir/article_20646_6b6322fe9f40ebe8877e67759568761c.pdf |
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