Zamri Hana Farizah, Mohd Ali Mohammad Ridhuan, Sha'ari Ahmad Izzan Irfan, Mohd Mazalan Nurul Husna, Ahmad Norazah, Nor Amdan Nur Asyura, Abdul Rahim Nusaibah, Deris Zakuan Zainy
Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.
Bacteriology Unit, Institute for Medical Research (IMR), Malaysian Ministry of Health, Seksyen U13 Setia Alam, Shah Alam, Selangor 40170, Malaysia.
MethodsX. 2025 Jan 10;14:103167. doi: 10.1016/j.mex.2025.103167. eCollection 2025 Jun.
Non-clinical pharmacokinetic-pharmacodynamic (PKPD) models are crucial in the initial design of drug-dosage regimens and in drug development but has rarely been employed for testing high-risk organisms due to stringent handling procedures. is classified as a Tier 1 select agent with international guidelines recommending this organism to be handled within a biosafety level 3 (BSL3) facility. Unfortunately, BSL3 facilities are not widely available in low-resource settings. This paper describes a detailed guide for setting up an pharmacodynamic infection model specific for testing outside BSL 3 laboratory. Briefly in this study,•All procedures involving active handling of live cultures were performed strictly inside a class II BSC in BSL-2 plus negative airflow laboratory.•The model was set to simulate -bacteremia treated with ceftazidime, a 1st-line anti-melioidosis drug with an approximate 2-hour half-life. Model validation was performed by simulating ceftazidime half-life.•For the pharmacodynamic study, ceftazidime was given as bolus injections at 8-hour intervals into the central culture chamber containing actively growing .
非临床药代动力学-药效学(PKPD)模型在药物剂量方案的初始设计和药物开发中至关重要,但由于处理程序严格,很少用于检测高风险生物体。 被列为一级选择生物制剂,国际指南建议在生物安全3级(BSL3)设施内处理该生物体。不幸的是,低资源环境中没有广泛可用的BSL3设施。本文描述了一个详细的指南,用于建立一个专门在BSL 3实验室外检测 的药效学感染模型。简要介绍本研究:•所有涉及活 培养物主动处理的程序均在BSL-2加负压气流实验室的二级生物安全柜内严格进行。•该模型设置为模拟用头孢他啶治疗的 菌血症,头孢他啶是一种一线抗类鼻疽病药物,半衰期约为2小时。通过模拟头孢他啶半衰期进行模型验证。•对于药效学研究,每隔8小时将头孢他啶以推注方式注入含有活跃生长的 的中央培养室。