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 of Candida albicans infection on VRCZ concentrations in a silkworm infection model. The VRCZ concentration at 12 h after injection in the Candida 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.

伏立康唑 (VRCZ) 是一种三唑类抗真菌剂，用于治疗和预防侵袭性真菌感染。VRCZ 的治疗药物监测在临床上得到广泛应用，因为在 VRCZ 暴露中通常观察到较大的个体间变异性。在与感染相关的潜在炎症反应期间，VRCZ 的血液水平升高。家蚕是评估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，我们使用家蚕研究了 VRCZ 的药代动力学参数，例如消除半衰期、清除率和分布体积。VRCZ的药代动力学参数是根据注射VRCZ后在家蚕血淋巴中的浓度确定的。发现在家蚕中 VRCZ 的消除半衰期与在人类中观察到的相似。此外，我们评估了在家蚕感染模型中对 VRCZ 浓度的白色念珠菌感染。白色念珠菌感染组注射后 12 h 的 VRCZ 浓度显着高于未感染组。在蚕感染模型中，我们能够重现炎症与 VRCZ 血液浓度之间的关系，正如在人类中观察到的那样。我们证明家蚕可以成为研究 VRCZ 药代动力学的有效替代模型动物。我们还表明，蚕可用于指示 VRCZ 中的基本感染和基于炎症的药代动力学变化，这通常在临床中观察到。