5 and 6 Drug interactions that result in an altered pharmacokinetics are mainly observed with those beta-blockers that are excreted via metabolism (Metoprolol and carvedilol). Hence, Metoprolol has a higher potential for drug interactions. Selleck Raf inhibitor Considering modulation of CYP2D6 by both of these two drugs, Duloxetine and Metoprolol, possible interaction at P-glycoprotein, this study was undertaken to evaluate the influence of Duloxetine on the pharmacokinetics of Metoprolol
in rat model. Metoprolol was obtained as a gift sample from Matrix Laboratories, Hyderabad (India). Duloxetine was obtained as a gift sample from Hetero Laboratories, Hyderabad (India). All HPLC grade solvents (acetonitrile, methanol and water) were procured from SD Fine chemicals, Mumbai, India. All other chemicals used were of analytical grade and purchased from local chemical agencies. HPLC (A Shimadzu Class VP series HPLC system) with two LC-10AT pumps, an SPD-10A variable wavelength programmable UV/Vis detector, an SCL-10A system controller was manufactured by DONG-IL Shimadzu Corporation, Kangnam-Ku, Seoul, Korea. Zodiac C8, 150 mm × 4.6 mm, 5 μm was used. The system was equipped with Class VP series version 6.12 software. Sonicator (Hwashin Technology, Seoul, Korea), Biofuge (Hearus instrument, Hanau, Germany), micropipettes,
tubes (Tarsons Products Pvt. Ltd, Kolkata, India) were used. Albino Wistar rats (National Institute of Nutrition, Hyderabad, India), of either sex, weighing 200–250 g, were selected. Animals were maintained under standard JQ1 laboratory conditions at 25 ± 2 °C, relative humidity 50 ± 15% and normal photoperiod (12 h
dark/12 h light). Commercial pellet diet (Rayon’s Biotechnology Pvt. Ltd, India) and water were provided ad libitum. The experimental protocol was approved by the Institutional Animal Ethics Committee of AMR Memorial College of Pharmacy on 04-05-2012 with protocol no: AMRMCP/IAEC/2012/13 and experiments were carried out as per the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) (Institutional CPCSEA registration number is CPCSEA/ORG/CH/2008/Reg. no. 1219). Wistar rats were randomly distributed into three groups of six animals in each group. Before doing, all experimental animals were Methisazone fasted for 18 h and but water was given ad libitum. After collection of initial blood samples, drugs were administered in the following order. Group I – Control (0.2 mL of 0.5% carboxy methyl cellulose (CMC) sodium; p.o.) In this study, both Metoprolol tartrate and Duloxetine hydrochloride were dissolved in distilled water. Pretreatment blood sample was collected at 0 h i.e. before treatment and then remaining all blood samples were from orbital sinuses into 2 mL Eppendorf tubes containing sodium citrate as anticoagulant. Plasma was separated by centrifugation at 5000 rpm/10 min and stored at −20 °C until further analysis.