A MULTIVARIATE INTERPOLATION APPROACH FOR PREDICTING DRUG LD50 VALUE

Year 2024, Volume: 48 Issue: 1, 20 - 33, 20.01.2024

Gül Karaduman , Feyza Kelleci Çelik

https://doi.org/10.33483/jfpau.1322948

Abstract

Objective: The present study aimed to develop a multivariate interpolation based on the quantitative structure-toxicity relationship (QSTR) that can accurately predict the oral median lethal dose (LD50) values of drugs in mice by considering five different toxicologic endpoints.
Material and Method: A mathematical model was created using a comprehensive dataset comprising LD50 values from 319 pharmaceuticals belonging to various pharmacological classes. We developed a polynomial model that can predict the range of LD50 values for pharmaceuticals. We employed a technique called two-variable polynomial interpolation. This method allowed us to estimate the approximate values of a function at any point within a two-dimensional (2D) space by utilizing a polynomial equation.
Result and Discussion: The resulting model demonstrated the ability to predict LD50 values for new or untested drugs, rendering it a valuable tool in the early stages of drug development. The Ghose-Crippen-Viswanadhan octanol-water partition coefficient (ALogP) and Molecular Weight (MW) were selected as suitable descriptors for building the best QSAR model. Based on our evaluation, the model achieved an overall success rate of 86.73%. Compared to traditional experimental methods for LD50 determination, this innovative approach offers time and cost efficiency while reducing animal testing requirements. Our model can improve drug safety, optimize dosage regimens, and assist decision-making processes during preclinical studies and drug development. This approach provided a reliable and efficient method for preliminary acute toxicity assessments.

Keywords

Data analysis, LD50, mathematical toxicology, multivariate interpolation, polynomial interpolation

İLAÇ LD50 DEĞERİNİ TAHMİN ETMEK İÇİN ÇOK DEĞİŞKENLİ BİR İNTERPOLASYON YAKLAŞIMI

Abstract

Amaç: Bu çalışmanın amacı, beş farklı toksikolojik sonucu dikkate alarak farelerde ilaçların oral median letal doz (LD50) değerlerini doğru bir şekilde tahmin edebilen, niceliksel yapı-toksisite ilişkisine (QSTR) dayalı çok değişkenli bir interpolasyon yöntemi geliştirmektir.
Gereç ve Yöntem: Farklı farmakolojik sınıflara ait 319 ilaca ait LD50 değerlerini içeren kapsamlı bir veri seti kullanılarak matematiksel bir model oluşturuldu. Farmasötiklerin LD50 değerlerinin aralığını tahmin edebilen bir polinom model geliştirdik. İki değişkenli polinom interpolasyon adı verilen bir teknik kullanarak bunu gerçekleştirdik. Bu yöntem, bir polinom denklemi kullanarak iki boyutlu bir uzayda herhangi bir noktadaki bir fonksiyonun değerlerini tahmin etmemizi sağladı.
Sonuç ve Tartışma: Elde edilen model, yeni veya denenmemiş ilaçlar için LD50 değerlerini tahmin etme yeteneğini gösterdi ve bu nedenle ilaç geliştirme sürecinin erken aşamalarında değerli bir araç olarak kullanılabilir. Değerlendirmemize göre, model genel başarı oranı olarak %86,73 olarak bulundu. LD50 değerinin belirlenmesinde kullanılan geleneksel deneysel yöntemlere kıyasla, bu yenilikçi yaklaşım zaman ve maliyet açısından avantajlı olup hayvan deneylerinin gerekliliğini azaltmaktadır. Modelimiz ilaç güvenliğini artırabilir, doz rejimlerini optimize edebilir ve ön klinik çalışmalar ve ilaç geliştirme sürecinde karar verme süreçlerine yardımcı olabilir. Bu yaklaşım, ön akut toksisite değerlendirmeleri için güvenilir ve etkili bir yöntem sunmuştur.

Keywords

Çok değişkenli interpolasyon, LD50, matematiksel toksikoloji, polinom interpolasyonu, veri analizi

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