TY  - JOUR
T1  - Chou-Talalay Metodu ile İlaç Kombinasyonlarının Analizi: Prensipler, Deneysel Tasarım Stratejileri ve Bilgisayar Yazılımıyla Analiz
TT  - Analysis of Drug Combinations with Chou-Talalay Method: Principles, Experimental Design Strategies, and Analysis with Computer Software
AU  - Özer, Bayram Oğuz
PY  - 2024
DA  - March
DO  - 10.57221/izmirtip.1288764
JF  - İzmir Tıp Fakültesi Dergisi
JO  - İzmir Tıp Fak. Derg.
PB  - University of Health Sciences
WT  - DergiPark
SN  - 2822-4833
SP  - 51
EP  - 60
VL  - 3
IS  - 1
LA  - tr
AB  - Şuana kadar, ilaç kombinasyonlarının analizi için çok sayıda çeşitli yöntem geliştirilmiştir. Bu metotlar arasından Chou-Talalay'ın kombinasyon indeksi teorisi artan bir popülerlik kazanmıştır ve yaygın kabul görmüştür. Chou-Talalay yöntemi, kütle-eylem yasasının medyan-etki prensibinden türetilen kombinasyon etkisi denklemine dayanır. İlaç etkileşimlerinin nicel analizi ve ilaç kombinasyonlarının simülasyonu için bilgisayar yazılım algoritması sağlar. Her bir ilacın ve kombinasyonlarının doz-etki eğrisinin potensini ve şeklini dikkate alır. CompuSyn yazılımı ile bilgisayar simülasyonu, in vitro veya in vivo çalışmalar için doz-etki eğrisini, medyan-etki grafiğini, kombinasyon indeksi grafiğini, izobologramı, doz-azaltma indeksi grafiğini ve poligonogramı gösterir. Bu derlemede, ilaç kombinasyon çalışmaları için teorik ve pratik bir kılavuz sağlamayı ve kütle-eylem yasası temelli teoriyi, deneysel tasarımı ve veri analizini açıklamayı amaçladık. Chou-Talalay’ın medyan-etki denklemi, ilaç kombinasyonlarının nicel analizi için kullanışlı ve pratik bir yöntemdir. Medyan-etki eşitliği in vitro, in vivo ve klinikte az sayıda deneysel veri kullanılmasına imkan verir. Medyan-etki denkleminin algoritmaları, küçük-ölçekli deneyler için daha az deneysel veri gereksinimi ve ilaç kombinasyonlarının analizine yönelik kantitatif çıkarımlar sağladığı için verimli, düşük maliyetli çalışma, ilaç keşfi ve klinik araştırmalarda etik planlamaya olanak sağlar. Yöntem, ilaç kombinasyonlarının analizinde en yaygın kullanılan metottur ve çok sayıda atıf almıştır. Bu çalışmanın ilaç kombinasyonlarının analizi için önemli bir referans teşkil edeceğine inanıyoruz.
KW  - Chou-Talalay
KW  - CompuSyn
KW  - İlaç kombinasyonu
KW  - Kombinasyon indeksi
KW  - Medyan-etki denklemi
N2  - Until now, a large number of various methods have been developed for the analysis of drug combinations. Among these methods, combination index theory of Chou-Talalay has gained increasing popularity and endured widespread acceptance. The Chou-Talalay method is based on the combination effect equation derived from the median-effect principle of the mass-action law. It provides quantitative analysis of drug interactions, and the algorithm for computer software for the simulation of drug combinations. It takes into account both the potency and the shape of the dose-effect curve of each drug alone and their combinations. Computer simulation using CompuSyn software displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. In this review, we aimed to provides a theoretical and practical guide for drug combination studies and delineates its essence in terms of the mass-action law based theory, experimental design and data analysis. Median-effect equation of Chou-Talalay is a useful and practical method for the quantitative analysis of drug combinations. The median-effect equation allows the use of few experimental data in vitro, in vivo, and in clinics. The algorithms of the median-effect equation enable efficient, low-cost study, drug discovery, and ethical planning in clinical research, as they provide less experimental data requirements for small-scale experiments and quantitative implications for the analysis of drug combinations. The method is the most widely used in the analysis of drug combinations and has received numerous citations. We believe that this study will constitute an important reference for the analysis of drug combinations.
CR  - 1.	Foucquier J, Guedj M. Analysis of drug combinations: current methodological landscape. Pharmacology Research & Perspectives. 2015;3:e00149.
CR  - 2.	Chou T-C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacological Reviews. 2006;58:621-81.
CR  - 3.	Pinto AC, Moreira JN, Simões S. Combination chemotherapy in cancer: Principles, evaluation and drug delivery strategies.  Current Cancer Treatment-Novel Beyond Conventional Approaches: IntechOpen; 2011.
CR  - 4.	Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. 2017;8:38022-43.
CR  - 5.	Özer B. Kolon kanseri tedavisi için yeni nanoterapötik modalitelerin geliştirilmesi. Edirne.: Doktora Tezi. Trakya Üniversitesi Fen Bilimleri Enstitüsü Biyoteknoloji ve Genetik Anabilim Dalı, 2021; 2021.
CR  - 6.	Chou T-C. The combination index (CI <1) as the definition of synergism and of synergy claims. Synergy. 2018;7:49-50.
CR  - 7.	Chou T-C. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Research. 2010;70:440-6.
CR  - 8.	Chou T, Martin N. CompuSyn for drug combinations: PC software and user’s guide: a computer program for quantitation of synergism and antagonism in drug combinations, and the determination of IC50 and ED50 and LD50 values. Paramus (NJ): ComboSyn; 2005. Available at: www.combosyn.com. 2005.
CR  - 9.	Chou T-C. Preclinical versus clinical drug combination studies. Leukemia & Lymphoma. 2008;49:2059-80.
CR  - 10.	Chou T-C, Hayball MP. CalcuSyn for windows: Multiple-drug dose-effect analyzer and manua. Biosoft, UK. 1996.
CR  - 11.	Chou T-C, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation. 1984;22:27-55.
CR  - 12.	Chou T-C. Combinatorial analysis of multiple substrate—multiple product enzyme reactions. Journal of Theoretical Biology. 1972;35:285-97.
CR  - 13.	Chou T-C. Relationships between inhibition constants and fractional inhibition in enzyme-catalyzed reactions with different numbers of reactants, different reaction mechanisms, and different types and mechanisms of inhibition. Molecular Pharmacology. 1974;10:235-47.
CR  - 14.	Chou T-C. Derivation and properties of Michaelis-Menten type and Hill type equations for reference ligands. Journal of Theoretical Biology. 1976;59:253-76.
CR  - 15.	Chou J, Chou T. Dose‐effect analysis with microcomputers: Quantitation of ED50, LD50, synergism, antagonism, low‐dose risk, receptor binding and enzyme kinetics. Computer software for Apple II series IBM-PC instruction manual. 1985:19-28.
CR  - 16.	Chou T, Hayball M. CalcuSyn for Windows: multiple-drug dose-effect analyzer and manual. Biosoft, Cambridge Place, Cambridge, United Kingdom. 1996.
CR  - 17.	Chou T-C. The mass-action law based algorithms for quantitative econo-green bio-research. Integrative Biology. 2011;3:548-59.
CR  - 18.	Chou T-C. On the determination of availability of ligand binding sites in steady-state systems. Journal of Theoretical Biology. 1977;65:345-56.
CR  - 19.	Chou TC, Talalay P. Generalized equations for the analysis of inhibitions of Michaelis‐Menten and higher‐order kinetic systems with two or more mutually exclusive and nonexclusive inhibitors. European Journal of Biochemistry. 1981;115:207-16.
CR  - 20.	Chou T-C, Talalay P. Analysis of combined drug effects: a new look at a very old problem. Trends in Pharmacological Sciences. 1983;4:450-4.
CR  - 21.	Özer BO. Sinerjistik ilaç kombinasyonlarının analizinde güncel matematiksel ve istatistiksel yöntemler. Journal of Faculty of Pharmacy of Ankara University. 2023;47:687-704.
CR  - 22.	Chou T-C, Motzer RJ, Tong Y, Bosl GJ. Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. JNCI: Journal of the National Cancer Institute. 1994;86:1517-24.
CR  - 23.	Chou T-C. Drug combination against xenograft tumors in nude mice: Experimental design, execution, and computerized simulation of synergism and antagonism. Cancer Research. 2008;68:4183-.
CR  - 24.	Chou T-C. Chemotherapeutic synergism, potentiation and antagonism. In: TC C, DC R, editors. Encyclopedia of Human Biology. Academic Press, New York. 1991. pp. 371-9.
UR  - https://doi.org/10.57221/izmirtip.1288764
L1  - https://dergipark.org.tr/en/download/article-file/3107891
ER  -