CURRENT MATHEMATICAL AND STATISTICAL METHODS IN THE ANALYSIS OF SYNERGISTIC DRUG COMBINATIONS

Öz

Objective: Combination drug therapy plays an important role in treating various deadly diseases such as cancer. When drugs are combined, synergistic, additive or antagonistic interactions occur. The determination of these interactions and the quantitative analysis of drug combinations are not simple. The lack of standardization in terminology, experimental protocols, and models as well as data analysis are major challenges. In this study, the current mathematical and statistical methods concerning the study and analysis of synergistic drug combinations are reviewed. Following, the pharmacological and mathematical concepts necessary to understand the widely used methods are also reviewed, and their advantages and disadvantages are discussed. Finally, the main issues to be considered in the analysis of drug combinations are explained. Result and Discussion: Because there is no optimal suitable model for all possible experimental conditions, we hope that the quantitative analysis of drug combinations will be facilitated by the collective use of the different approaches discussed here. We believe that this study will serve as a reference for the analysis of drug combinations.

Anahtar Kelimeler

• Bliss independence
• Chou-talalay
• drug combination
• combination index
• loewe synergism

SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER

Öz

Amaç: İlaç kombinasyon tedavisi, kanser gibi çeşitli ölümcül hastalıkların tedavisinde önemli rol oynamaktadır. İlaçlar kombine edildiğinde sinerjistik, additif veya antagonistik etkileşimler meydana gelir. Bu etkileşimlerin tanımlanması ve ilaç kombinasyonlarının kantitatif analizi basit değildir. Terminoloji, deneysel protokoller ve modellerin yanı sıra veri analizinde standardizasyon eksikliği başlıca sorunlardır. Bu çalışmada, sinerjistik ilaç kombinasyonlarının incelenmesi ve analizi ile ilgili mevcut matematiksel ve istatistiksel yöntemler derlenmiştir. Takibinde, yaygın kullanılan yöntemleri anlamak için gerekli olan farmakolojik ve matematiksel kavramlar da derlenmiş, avantaj ve dezavantajları tartışılmıştır. Son olarak ilaç kombinasyonlarının analizinde dikkat edilmesi gereken temel konular açıklanmıştır. Sonuç ve Tartışma: Muhtemel tüm deneysel koşullar için uygun optimum bir model olmadığı için, ilaç kombinasyonlarının kantitatif analizinin, burada tartışılan farklı yaklaşımların kollektif kullanımı ile kolaylaşacağını umuyoruz. Bu çalışmanın ilaç kombinasyonlarının analizi için bir referans teşkil edeceğine inanıyoruz.

Anahtar Kelimeler

• Bliss bağımsızlığı
• chou-talalay
• ilaç kombinasyonu
• kombinasyon indeksi
• loewe sinerjizm

Kaynakça

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