Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University.
Department of Laboratory Medicine, The Jikei University Kashiwa Hospital.
Biol Pharm Bull. 2019 Dec 1;42(12):2089-2094. doi: 10.1248/bpb.b19-00652. Epub 2019 Sep 18.
The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.
本研究旨在通过大样本谷浓度回顾性分析，研究日本血液恶性肿瘤与非恶性肿瘤患者万古霉素（VAN）的药代动力学差异。共收集 261 例血液恶性肿瘤患者和 261 例非恶性肿瘤患者的临床资料，包括患者背景、VAN 剂量及采用经验贝叶斯法估算的 VAN 药代动力学参数。结果显示，与非恶性肿瘤患者相比，血液恶性肿瘤患者的 VAN 清除率更高，消除半衰期更短。此外，采用倾向评分匹配调整混杂因素的多元回归分析显示，VAN 清除率与血液恶性肿瘤呈正相关。综上所述，由于血液恶性肿瘤患者的 VAN 清除率增加，VAN 的血药浓度低于预期，这可能导致在低剂量使用 VAN 时耐药菌的存活。这些结果提示，对于血液恶性肿瘤患者，建议早期监测 VAN 水平，以在不产生副作用的情况下维持预期疗效。
