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Öğe Application of HPLC to investigate the physicochemical properties and intestinal permeability of Ketoprofen(Bentham Science Publishers B.V., 2017) Kaynak M.S.; Çelebier M.; Akgeyik E.; Sahin S.; Altınöz S.Introduction: The main objective of this study was to investigate the effect of pH on the solubility and intestinal permeability of ketoprofen by using HPLC. Ketoprofen is a slightly soluble acidic drug, and its solubility in aqueous phase is affected by pH changes dramatically. However, there is no data in the literature to support whether this pH dependent water solubility of ketoprofen will influence its absorption/bioavailability. Method: In this study, the distribution-coefficient (log D) of ketoprofen at various pH values between 4.5 and 7.5 were investigated using HPLC, and then it was made an attempt to correlate the log D values with the intestinal permeability values. For this reason, in vivo intestinal permeability studies were performed at pH 4.5 and pH 7.5. The concentrations of model and reference compounds and also the blank buffers passed though the rat intestine were analyzed by means of a validated HPLC method. Result: A nonlinear relationship was found between the results of in vitro and in vivo studies indicating that the diffusion of ketoprofen was not only related with passive diffusion, but also could be related with active transport. © 2017 Bentham Science Publishers.Öğe Determination of in vitro dissolution profiles of amlodipine besylate and olmesartan medoxomil using a new "HPLC method"(Syscom 18 SRL, 2013) Kaynak M.S.; Çelebier M.; Sahin S.; Altinöz S.The aim of this study was to develop an HPLC method for simultaneous determination of these active compounds and to apply this method to determine the dissolution of AML and OLM from a commercially available tablet. Valsartan (VAL) was used as an internal standard (IS). Separation of AML, OLM and VAL was performed using Phenomenex C18 column (Luna 5 ?, 100A, 250x4.6 mm; California, USA) protected with a Phenomenex C18 guard column (4.0x3.0 mm; California, USA). The chromatographic separation operated isocratically at room temperature using a mobile phase consisted of phosphate buffer (pH 4.0,0.04 mol/L):methanol: acetonitrile (40:45:15, v/v/v) delivered at a flow rate of 0.8 mL/min and injection volume was 10 ?L. The diode array detector was set at 234 nm and 205 nm wavelengths for the quantirication of AML and OLM respectively. In vitro dissolution studies revealed that 85% of the labeled amounts of AML and OLM were released within 25 min from their fixed combination tablet dosage form. The developed HPLC method was validated according to the ICH guidelines and it is proposed for dissolution studies of the combination dosage forms of these compounds.Öğe Evaluation of Pharmacokinetics and Biodistribution of Targeted Nanoparticles(Taylor and Francis, 2021) Ates M.; Izat N.; Kir F.; Gulsun T.; Sahin S.Nanotechnology attracts more attention day by day in the field of pharmacy as in many fields. This chapter discusses the biodistribution and pharmacokinetic (PK) properties of nanoparticles, the factors affecting these properties, and studies for assessment. Physiologically based pharmacokinetic modeling (PBPK) is a powerful descriptive tool that mechanistically describes the PK and/or pharmacodynamic behaviors of drugs by using models and simulations with combined considerations of physiology, population, and drug characteristics. The chapter highlights PBPK applications for the PK evaluation and formulation development of nanoparticles. PBPK models are valuable tools to understand and predict the in vivo reflection of changes in formulation design and development factors. Using the dissolution- and distribution-based model, the observed in vivo situation was described successfully by establishing an in vitro–in vivo correlation between physicochemical characteristics of the formulation and clinical data. © 2022 Jenny Stanford Publishing Pte. Ltd.Öğe Interaction of Statins with Grapefruit Juice(Society of Pharmaceutical Sciences of Ankara (FABAD), 2023) Ateş M.; Sahin S.Grapefruit juice, which discovered to interact with felodipine for the first time, is now known to interact with more than 80 drugs. Statins are among the drugs that interact with grapefruit juice. Grapefruit juice-statin interactions were first investigated in 1998 in human pharmacokinetic studies with lovastatin and simvastatin. The pharmacokinetic and pharmacodynamic basis of the interaction has been extensively investigated in studies. Flavonoids and furanocoumarins, the main components of grapefruit juice, have been reported to cause drug interactions. Furthermore, statin-grapefruit juice interactions occur mostly through inhibition of cytochrome-3A4 (CYP3A4), to a lesser extent through inhibition of P-glycoprotein (Pgp) and organic anion transporting polypeptides (OATPs). Changes in plasma drug levels as a result of interaction may increase the side-effect of statins or reduce their therapeutic efficacy. Therefore, patients using statins are generally advised to avoid grapefruit juice consumption. © 2023 Society of Pharmaceutical Sciences of Ankara (FABAD). All rights reserved.Öğe A multicenter cross-sectional study to evaluate the clinical characteristics and nutritional status of children with cerebral palsy(Elsevier Ltd, 2018) Aydin K.; Aydin K.; Akbas Y.; Unay B.; Arslan M.; Cansu A.; Sahin S.Background & aims: This study was designed to assess clinical characteristics and nutritional status of pediatric outpatients with cerebral palsy (CP) and to determine prevalence of malnutrition based on physicians’ clinical judgment and on anthropometric data in relation to percentile reference values. Methods: A total of 1108 pediatric neurology outpatients (mean ± SEM age: 7.2 ± 0.1 years, 59.3% were males) diagnosed with CP were included in this cross-sectional, non-interventional multicenter single-visit study conducted between October 2015 and July 2016 at 20 centers across Turkey. Data on patient and CP characteristics, concomitant nonneuromotor impairments and gastrointestinal disorders as well as anthropometrics, outcome of nutritional status assessment (via physicians’ clinical judgment and Gomez classification and Waterlow classification of anthropometric data) and physician's view on nutritional care in CP patients were collected at a single visit. Results: The most common CP etiology was asphyxia (62.5%). The most common clinical category was spastic CP (87.5%) with quadriplegic (54.0%) topography and level V gross motor dysfunction (45.4%) in most of patients. The prevalence of malnutrition was considered to be 57.2% based on physicians’ clinical judgment, while shown to be 94.3% (3rd degree in 86.7%) according to Gomez classification of Neyzi weight for age (WFA) percentiles and to be 91.3% (severe in 88.3%) according to Waterlow classification of Neyzi height for age (HFA) percentiles. Conclusions: In conclusion, our findings revealed high prevalence of malnutrition, while also emphasize the likelihood of overestimation of malnutrition in children with CP when anthropometric assessment was based on use of growth charts for general pediatric population. This large-scale survey provided valuable data regarding nutritional assessment practice and malnutrition prevalence among children with CP in Turkey, which may be utilized for future proactive strategies in the prevention and treatment of malnutrition in this population. © 2018 European Society for Clinical Nutrition and MetabolismÖğe Physicochemical and pharmacokinetic properties of acyclovir(Nova Science Publishers, Inc., 2023) Sahin S.; Ates M.Acyclovir (2-amino-9-(2-hydroxyethoxymethyl)-1H-purin-6-one) is an antiviral drug that is a guanine nucleoside analogue. The molecule was discovered in 1974. Clinical trials started in 1977, and it was marketed for the first time in 1981. Since then, acyclovir has become one of the most used antiviral drugs worldwide. It was included in the WHO Model List of Essential Medicines in October 2013. It is used in the treatment of herpes simplex viruses, varicella-zoster virus, Epstein-Barr virus and cytomegalovirus. After acyclovir uptake, it is converted to acyclovir monophosphate by thymidine kinase. Since this transformation occurs in infected cells, the specificity of drug increases. Cellular enzymes convert the acyclovir monophosphate to acyclovir triphosphate. Acyclovir triphosphate inhibits DNA polymerase, inhibiting DNA synthesis and viral replication. Acyclovir is commercially available as tablets (200 mg, 400 mg, and 800 mg), oral suspension (400 mg/5 mL), topical cream (5%), intravenous injection (25 mg/mL, sodium salt), and ophthalmic ointment (3%). Acyclovir is slightly soluble in water (1.2-1.6 mg/mL at 22-25°C) and its solubility affected by pH (2.3 mg/mL at pH 5.8). Although aqueous solubility of acyclovir is more than 100 mg/mL at 25°C, it is nonionic at pH 7.4 (maximum solubility 2.5 mg/mL at 37°C). Acyclovir is an amphoteric molecule with two pKa values (2.27 and 9.25). Acyclovir is classified as Class III (high solubility, low permeability/poor metabolism) drug according to Biopharmaceutics Classification System (BCS), and Class IV for the Biopharmaceutics Drug Disposition Classification System (BDDCS). Absorption of acyclovir is slow, variable and insufficient, and its oral bioavailability is low (10-30%). Maximum plasma concentration is reached within 1.5-2.5 hours. After multiple dosing, steady-state concentration is reached within 1-2 days. Acyclovir is widely distributed in many body tissues including lung, brain, kidney, spleen, heart, liver, muscle, placenta and uterus. The protein binding of acyclovir is 9-33% and the volume of distribution is 48 L/1.73 m2. The main route of elimination is renal excretion as unchanged drug via glomerular filtration and tubular secretion. Acyclovir is metabolized in the liver (8-14%) and converted to its pharmacologically inactive metabolite 9-(carboxymethoxy)methyl] guanine. The half-life is about 2.5 hours. Acyclovir is well tolerated, but some adverse effects such as nausea, vomiting, diarrhea, and headache may occur depending on the route of administration. In addition, skin rash and contact dermatitis can be seen in topical applications. Intravenous infusion may cause nephropathy and phlebitis due to crystallization in the renal tubules. Acute renal failure can develop very rarely. In this chapter, physicochemical and pharmacokinetic properties of acyclovir will be given in detail. © 2024 Nova Science Publishers, Inc.
