Availability, Use and Development of Animal Models for the Assessment of Drug-Drug Interactions and Safety of Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs) are novel, direct acting drugs that are selective for either thrombin or activated factor X. Due to their obvious benefits for patients (broader therapeutic window, are not routinely monitored etc.), they are increasingly used as an alternative to vitamin K antagonists. One of the major indications for the use of DOACs is the stroke prevention in patients with atrial fibrillation (AF). Although, the DOAC use becomes extensive in the clinical area especially cardiology, many drug drug interactions occur when DOACs are used with other drugs. Also, the safety profile of DOACs is still to be investigated. Animal models can be used to investigate the drug drug interactions and safety of DOACs under standart laboratory conditions. Unfortunately, there is not sufficient data that investigates the drug drug interactions and safety of DOACs in animal models. The focus of this review will be the availability, use and development of animal models to assess drug drug interactions and safety profile of DOACs.

Yeni Nesil Oral Antikoagulanların İlaç İlaç Etkileşimleri ve Güvenliliğinin Değerlendirilebilmesi İçin Hayvan Modellerinin Geliştirilmesi, Kullanımı ve Bulunabilirliği

Direkt oral antikoagulanlar (DOAK’lar), yeni, thrombine veya aktive faktör Xa’ya selektif olan direkt etkili ilaçlardır. Bu yeni oral antikoagulan ilaçların, klasik antikoagulan ilaçlara göre hastalar açısından çok sayıda avantajları vardır (izleme ihtiyacının olmaması, geniş tedavi penceresi vbg.). Yakın geçmişte, direkt oral antikoagulanlar, tromboembolizmi önleme ve tedavisinde K vitamini antagonistlerine alternatif olarak sunulmuşlardır. DOAKların ana kullanım alanı, atrial fibrilasyonlu hastalarda inmenin önlenmesidir. Ancak, öte yandan, DOAK’ların diğer ilaçlar ile kombine kullanımı sırasında ilaç-ilaç etkileşimleri oluşabilmekte ve güvenlilik profilleri henüz yeterli düzeyde bilinmemektedir. Günümüzde, DOAK’ların ilaç-ilaç etkileşimi ve güvenliliğini araştırmada kullanılan hayvan modelleri henüz yeterli değildir. Bu derlemenin amacı, DOAK’ların ilaç-ilaç etkileşimi ve güvenliliğini araştıran hayvan modellerinin daha da geliştirilmesi, kullanımı ve bulunabilirliğidir.

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