Izumisawa Tomohiro, Wakui Nobuyuki, Kaneko Tomoyoshi, Soma Masakazu, Imai Masahiko, Saito Daisuke, Hasegawa Hideo, Horino Tetsuya, Takahashi Noriko
Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University.
Department of Laboratory Medicine, The Jikei University Kashiwa Hospital.
Biol Pharm Bull. 2020 Jul 1;43(7):1081-1087. doi: 10.1248/bpb.b20-00083. Epub 2020 Apr 14.
Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.
万古霉素（VAN）是一种用于治疗多种细菌感染的抗菌药物，其肾毒性发生率较高。我们基于大规模的谷浓度回顾性研究了万古霉素的药代动力学，并确定了实体恶性肿瘤患者与非恶性肿瘤患者之间的药代动力学差异。分析了162例实体恶性肿瘤患者和261例非恶性肿瘤患者的数据，包括患者背景、万古霉素剂量和万古霉素的药代动力学。我们未能检测到这两组之间万古霉素清除率值或较短消除半衰期的差异。相比之下，通过倾向评分调整混杂因素后的多元回归分析表明，在每个阶段，万古霉素清除率相对于实体恶性肿瘤显著增加。我们得出结论，实体恶性肿瘤患者的万古霉素清除率增加，且万古霉素血药浓度低于预期。这些结果表明，对实体恶性肿瘤患者早期监测万古霉素水平可能对于在无副作用的情况下维持预期疗效至关重要。
