Pharmacokinetics of voriconazole and its alteration by Candida albicans infection in silkworms
Pharmacokinetics of voriconazole and its alteration by Candida albicans infection in silkworms
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DOI：
10.1038/s41429-021-00428-z
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发表时间：
2021-05-27
影响因子：
3.3
通讯作者：
Sugita，Takashi
中科院分区：
文献类型：
--
作者：
Yasu，Takeo;Matsumoto，Yasuhiko;Sugita，Takashi
伏立康唑（VRCZ）是一种三唑类抗真菌药，用于治疗和预防侵袭性真菌感染。VRCZ的治疗药物监测被广泛应用于临床，因为在VRCZ暴露中通常观察到较大的个体间变异性。VRCZ的血液水平在潜在的炎症反应期间增加，这与感染有关。蚕是用于评价化合物的药代动力学和毒性的有用实验动物。在这项研究中，我们研究了药代动力学参数，如消除半衰期，清除率和分布容积的VRCZ使用家蚕。以家蚕血淋巴中的药物浓度为基础，测定了家蚕注射VRCZ后的药代动力学参数。VRCZ在家蚕中的消除半衰期与在人体中观察到的相似。此外，我们评估了白色念珠菌感染对家蚕感染模型中VRCZ浓度的影响。白念珠菌感染组注射后12 h的VRCZ浓度显著高于非感染组。在蚕感染模型中，我们能够再现炎症和VRCZ血液浓度之间的关系，如在人类中观察到的那样。我们证明，蚕可以是一个有效的替代模型动物研究VRCZ的药代动力学。我们还表明，蚕可以用来指示基本的感染和炎症为基础的药代动力学变化的VRCZ，这是通常在临床上观察到的。
Voriconazole (VRCZ) is a triazole antifungal agent used for the treatment and prophylaxis of invasive fungal infections. Therapeutic drug monitoring of VRCZ is widely applied clinically because of the large inter-individual variability that is generally observed in VRCZ exposure. The blood levels of VRCZ are increased during an underlying inflammatory reaction, which is associated with infections. Silkworms are useful experimental animals for evaluating the pharmacokinetics and toxicity of compounds. In this study, we investigated the pharmacokinetic parameters, such as elimination half-life, clearance, and distribution volume of VRCZ using silkworms. The pharmacokinetic parameters of VRCZ were determined based on the concentrations in silkworm hemolymph after injection of VRCZ. The elimination half-life of VRCZ in silkworms was found to be similar to that observed in humans. In addition, we assessed the impact ofCandida albicansinfection on VRCZ concentrations in a silkworm infection model. The VRCZ concentration at 12 h after injection in theCandida albicans-infected group was significantly higher than that in the non-infected group. In the silkworm infection model, we were able to reproduce the relationship between inflammation and VRCZ blood concentrations, as observed in humans. We demonstrate that silkworms can be an effective alternative model animal for studying the pharmacokinetics of VRCZ. We also show that silkworms can be used to indicate essential infection and inflammation-based pharmacokinetic variations in VRCZ, which is usually observed in the clinic.