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Öğe Bioavailability file: Amlodipine(Ankara University, 2011) Kaynak M.S.; Bogacz A.; Stelmasi?ski M.; Şahin S.Amlodipine (AML), a third-generation dihydropiridin, is a long-acting L-calcium channel blocker used in the treatment of hypertension and angina pectoris. It exerts its effects by blocking the voltage-dependent L-calcium channels and binding to both dihydropiridin and nondihydropiridin binding sites. AML is well absorbed (96%) after oral administration and its bioavailability is between 64-90%. Its volume of distribution is about 16 to 21 L/kg and protein binding is 98% after oral administration. AML is extensively metabolized in the liver and its elimination from the plasma is biphasic with a terminal half-life of 30 to 50 h. It is excreted by renal route about 60%. According to Biopharmaceutics Classification System, AML is classified as class I drug by WHO. In this review physicochemical properties, pharmacology, analytical methods, pharmacokinetics and bioavailability of amlodipine are discussed.Öğe Determination of amlodipine and furosemide with newly developed and validated rp-hplc method in commercially available tablet dosage forms(Hacettepe University, Faculty of Pharmacy, 2012) Şimşek F.O.; Kaynak M.S.; Şanlı N.; Şahin S.The aim of this study was to develop a new, fast, reliable and validated RP-HPLC method for the simultaneous determination of amlodipine and furosemide in tablet dosage forms. A C18 column (Fortis™ 250x4.60 mm 5 ?m) which was heated at 45oC during the analysis, was used for the separation and quantification of these drugs. The mobile phase consisted of water (15 mM o-phosphoric acid, pH 5.0) and acetonitrile (50:50 v/v). Analyses were run at a flow rate 1.0 mL.min-1 and UV detector was set at 238 nm. The injection volume was 20 ?L and total run time for an assay was approximately 5 min. The developed method was validated according to the ICH guideline. For the application of the proposed RP-HPLC method, commercially available four different AML containing tablets (one reference (Norvasc) and three generic (Dilapin, Monovasc, Penvasc) tablets) and commercially available two different FSM containing tablets (one reference (Lasix) and one generic (Desal) tablet) were obtained from the market and analyzed for their drug content. Under the given chromatographic conditions, AML and FSM were eluted at 4.28 and 3.68 min., respectively. The method was linear in the concentration range of 1.0 to 16.0 ?g.mL-1 and 0.1 to 12.0 ?g.mL-1 for AML and FSM, respectively with a correlation coefficient >0.999. LOD and LOQ were 0.642 ?g.mL-1 and 2.139 ?g.mL-1 for AML 0.010 ?g.mL-1 and 0.031 ?g.mL-1 for FSM, respectively. Under the conditions used, the analysis completely fulfilled the system suitability test limits suggested by FDA for the quantitative chromatographic methods. The method was successfully applied for the analysis of these drugs in commercially available tablets. © 2012, Hacettepe University, Faculty of Pharmacy. All rights reserved.Öğe Effect of intratechal morphine on postoperative stress response and postoperative analgesic requirements on cardiac patients in major abdominal surgery(2000) To?al T.; Türköz A.; Durmuş M.; Şahin S.; Yilmaz S.; Ersoy M.Ö.This study investigated the use of single dose intratechal (IT) morphine on cardiac patients undergoing major abdominal surgery and its effect on postoperative stress response, hemodynamic response and postoperative analgesic requirements. ASA class III 20 patients were randomized to receive either 10 ?g/kg of intratechal morphine or control group. Induction were performed by fentanyl 5 ?g/kg, thiopentone 2-4 mg/kg and vecuronium 0.08 mg/kg and anaesthesia was maintained by 33% N2O/O2 mixture with sevoflurane. There were no significant differences in the serum cortisol, glucose, BUN, creatinine, ALP, ALT, AST, CK, CK-MB concentrations recorded in the two groups pre and postoperatively. Cortisol, CK and CK-MB concentrations increased in both groups postoperatively. Plasma glucose concentrations increased in control group postoperatively. There were no significant differences of hemodynamic parameters between the two groups. Analgesic requirements of control group increased postoperatively comparing IT group. Three patients died postoperatively, other side effects were clinically insignificant. In conclusion IT morphine had no effect upon hemodynamic response, did not inhibit the stress response to surgery perioperatively on cardiac patients but we demonstrated the decrease of the postoperative analgesic requirements.Öğe Permeability enhancers used to increase intestinal absorption(Hacettepe University, Faculty of Pharmacy, 2013) Ateş M.; Kaynak M.S.; Şahin S.Drugs are administered through various routes to obtain systemic effect. Of these, the most commonly used route of administration is the oral route. Following oral administration, the drug has to pass through several biological membranes until it reaches the site of effect. The most important one among these membranes is the intestinal epithelium. Absorption through the intestinal epithelium occurs mainly by two mechanisms. These mechanisms are absorption through the epithelial cell membranes (transcellular route) and absorption through the tight junctions between epithelial cells. Transport of molecules through the tight junctions is called as paracellular (intercellular) transport. The most effective way to improve drug absorption by regulating paracellular permeability is the structural organization of tight junctions. It is reported that some substances such as polymers, surfactants increase the absorption of paracellulary transported drugs across membranes by means of various mechanisms. These substances are also known as permeation enhancers. In this review, physicochemical peroperties of permeability enhancers and their mechanism of effect to increase intestinal absorption were discussed. Also various examples were given for these permeability enhancers and the studies counducted using these substances were evaluated. © 2013, Hacettepe University, Faculty of Pharmacy. All rights reserved.Öğe Simultaneous determination of acyclovir, metoprolol and phenol red by a RP-HPLC method for intestinal perfusion studies(Hacettepe University, Faculty of Pharmacy, 2015) Ateş M.; Kaynak M.S.; Şahin S.Intestinal perfusion (SPIP) technique is one of the most commonly used techniques to determine the intestinal permeability of a drug. In perfusion studies, metoprolol (as tartrate) and phenol red are widely used as a refer- ence compounds to evaluate the permeability coefficient of the compound of interest (acyclovir in this study). The aim of our study was to develop and validate a reversed-phase liquid chromatographic method for the simultan- eous determination of acyclovir, metoprolol and phenol red for use in intes- tinal perfusion studies. The analysis was performed on a C18 column (4.6 mm x 250 mm, 5 ?m) using a mobile phase consisting of methanol:0.0125 M potassium dihydrogen phosphate buffer (55:45, v/v; pH 7.0). Method was validated according to the FDA guidelines for selectivity, sensitivity, linearity, precision, accuracy, stability. All calibration curves were linear (r2> 0.999). Lower limit of quantitation was 0.04 ?g/mL for acyclovir, 0.02 ?g/mL for metoprolol, 0.01 ?g/mL for phenol red. Detection limit was 0.01 ?g/mL for acyclovir 0.002 ?g/mL for metoprolol, 0.003 ?g/mL for phenol red. Precision and accuracy results of the method fulfilled the required limits. This newly developed and validated method can be readily used on a routine basis for the standardization of in situ intestinal permeability experiments. © 2015, Hacettepe University, Faculty of Pharmacy. All rights reserved.
