Yamamoto Takaaki, Kawada Kei, Sato Chiemi, Tai Tatsuya, Yamaguchi Kazunori, Sumiyoshi Kenta, Tada Atsushi, Kurokawa Naohiro, Motoki Takahiro, Tanaka Hiroaki, Kosaka Shinji, Abe Shinji
Department of Clinical Pharmacy Practice Pedagogy, Tokushima University Graduate School of Biomedical Sciences.
Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences.
Biol Pharm Bull. 2024;47(12):2021-2027. doi: 10.1248/bpb.b24-00485.
Effective blood sampling times, beyond trough and peak levels, have not been determined for estimating vancomycin's area under the concentration-time curve (AUC) using the Bayesian software. The aim of this study was to evaluate the accuracy of AUC estimation at different blood sampling times during the same dosing interval at steady state utilizing data from a prior phase I trial of vancomycin. Six healthy adult participants were sampled following intravenous administration of 1 g vancomycin for 1.5 h every 12 h. The AUC was estimated using four software packages and four population pharmacokinetic models. Accuracy was assessed using bias (difference between the estimated and reference AUC) and imprecision (absolute percentage difference between the estimated and reference AUC). The accuracy varied with the sampling time. The optimal two-point sampling times were determined to be 2.5 and 5.5 h post-injection using software packages for EasyTDM, Practical AUC-guided therapeutic drug monitoring (TDM), and Anti-MRSA Agents TDM Analysis Software (incorporating Rodvold, Yamamoto, and Yasuhara models). In these estimations, the mean bias (range, -1.7 to 9.5 µg·h/mL) was unbiased and the mean imprecision (range, -3.0% to 5.0%) was precise. The optimal one-point sampling time was 5.5 h post-injection for Anti-MRSA Agents TDM Analysis Software, which incorporated the Yamamoto and Yasuhara models. In conclusion, optimal blood sampling times may vary depending on the software and model used. Our findings suggest that identifying specific sampling times could improve the efficacy of TDM in clinical practice.
使用贝叶斯软件估算万古霉素浓度-时间曲线下面积(AUC)时,除谷值和峰值水平外,有效采血时间尚未确定。本研究的目的是利用先前一项万古霉素I期试验的数据,评估稳态下相同给药间隔内不同采血时间AUC估算的准确性。六名健康成年参与者每12小时静脉注射1g万古霉素,持续1.5小时,随后进行采血。使用四个软件包和四个群体药代动力学模型估算AUC。使用偏差(估算的AUC与参考AUC之间的差异)和不精密度(估算的AUC与参考AUC之间的绝对百分比差异)评估准确性。准确性随采样时间而变化。使用EasyTDM软件包、实用AUC指导的治疗药物监测(TDM)以及抗MRSA药物TDM分析软件(包含Rodvold、Yamamoto和Yasuhara模型)确定最佳两点采样时间为注射后2.5小时和5.5小时。在这些估算中,平均偏差(范围为-1.7至9.5µg·h/mL)无偏差,平均不精密度(范围为-3.0%至5.0%)精确。对于包含Yamamoto和Yasuhara模型的抗MRSA药物TDM分析软件,最佳单点采样时间为注射后5.5小时。总之,最佳采血时间可能因所使用的软件和模型而异。我们的研究结果表明,确定特定的采样时间可以提高临床实践中TDM的疗效。