Antibakteriyel İlaçların Farmakokinetik/Farmakodinamik Entegrasyonu Üzerine Metodolojik Bir İnceleme

Antimikrobiyal ajanların uygun olmayan şekillerde kullanımı, bakterilerin ilaçlara direncine ve bakteri ekolojisinde değişikliklere neden olabilir. Özellikle çoklu ilaca dirençli bakterilerin ortaya çıkması, ilaçların antibakteriyel etkinliğini ciddi şekilde etkilemekte ve bu durum insan ve hayvanların sağlığını ve yaşamını tehdit etmektedir. Farmakokinetik/Farmakodinamik (PK/PD) modeller, PK ve PD verileri ile antibakteriyel etki arasındaki ilişkiyi analiz etmek için kullanılabilmektedir. PK/PD modelleri, dozaj rejimlerinin optimizasyonu, yeni ilaçların geliştirilmesi, duyarlılık sınır değerlerinin belirlenmesi ve dirençli mutantların analizleri için değerli rehberlik sağlarlar. PK/PD entegrasyonunun temel modelleri in vitro PK/PD, ex vivo PK/PD ve in vivo PK/PD’dir. Bu modellerin her birinin kendine göre avantajları ve dezavantajları vardır. Bu nedenle, uygun PK/PD modelinin nasıl seçileceğinin bilinmesi, doğru PK/PD verilerinin elde edilmesinde büyük bir etkiye sahiptir. Bu derlemede, yaygın olarak kullanılan PK/PD yöntemlerini açıklamaktayız. Böylelikle, ilaç rejimlerini optimize etmek ve ilaca dirençli bakteriyel enfeksiyonları önlemek ve kontrol etmek için bir referans sağlamaktayız.

A Methodological Review on the Pharmacokinetic/Pharmacodynamic Integration of Antibacterial Drugs

Inappropriate application of antimicrobial agents can result in resistance by bacteria to drugs and changes in bacterial ecology. In particular, the emergence of multi-drug resistant bacteria seriously aff ects the antibacterial effi cacy of drugs, which threatens the health and lives of humans and animals. Pharmacokinetic/Pharmacodynamic (PK/PD) models can be used to analyze the relationship between PK and PD data and the antibacterial eff ect. PK/PD models provide valuable guidance for optimization of dosage regimens, development of new drugs, setting of susceptibility breakpoints, and analyses of resistant mutants. Th e main models of PK/PD integration are in vitro PK/PD, ex vivo PK/PD, and in vivo PK/PD. Each of these models has its own advantages and disadvantages. Hence, knowing how to choose the appropriate PK/PD model has a huge infl uence on obtaining accurate PK/PD data. In this review, we describe the commonly used PK/PD methods. In this way, we provide a reference for optimizing drug regimens and preventing and controlling drug-resistant bacterial infections.

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