PDF(Pubmed)
Abstract：
UNASSIGNED: Dalbavancin is a long-acting lipoglycopeptide antibiotic that is increasingly utilized for infections that require prolonged treatment durations despite the lack of Food and Drug Administration approval for these indications. There is no consensus regarding optimal dosing of dalbavancin for these infections and no available pharmacokinetic studies to identify optimal dosing for long-term use.
UNASSIGNED: An in silico pharmacokinetic simulation was performed to assess the predicted dalbavancin concentration resulting from commonly utilized dosing regimens, in addition to modified regimens. The primary endpoint evaluated was days of median 24-hour free area under the curve over the minimum inhibitory concentration (AUC/MIC) >27.1, the established PK target.
UNASSIGNED: A dosing regimen of 1500 mg on day 0 and day 7 resulted in median AUC/breakpoint value above the target for 57 days (lower 95% confidence interval [CI], 37 days). A modified regimen of 1500 mg on day 0 and day 21 resulted in an additional 11 days of median AUC/breakpoint target attainment. The other standard dosing regimen modeled was 1000 mg on day 0, then 500 mg weekly for 5 doses. This regimen achieved the AUC/breakpoint target for 76 days (lower 95% CI, 59 days). This regimen was modified to 1000 mg on day 0, then 500 mg on days 14 and 28, which shortened the median effective treatment duration by 14 days but required 3 fewer doses.
UNASSIGNED: These simulated results, when combined with the favorable observational data, support the use of commonly reported dalbavancin regimens for prolonged therapy durations. In addition, these pharmacokinetic/pharmacodynamic data support extending the dosing interval beyond the frequently reported weekly regimens, which should be investigated further with a clinical trial.
UNASSIGNED: An in silico pharmacokinetic simulation was performed to assess the predicted dalbavancin concentration resulting from commonly utilized dosing regimens, in addition to modified regimens. The primary endpoint evaluated was days of median 24-hour free area under the curve over the minimum inhibitory concentration (AUC/MIC) >27.1, the established PK target.
UNASSIGNED: A dosing regimen of 1500 mg on day 0 and day 7 resulted in median AUC/breakpoint value above the target for 57 days (lower 95% confidence interval [CI], 37 days). A modified regimen of 1500 mg on day 0 and day 21 resulted in an additional 11 days of median AUC/breakpoint target attainment. The other standard dosing regimen modeled was 1000 mg on day 0, then 500 mg weekly for 5 doses. This regimen achieved the AUC/breakpoint target for 76 days (lower 95% CI, 59 days). This regimen was modified to 1000 mg on day 0, then 500 mg on days 14 and 28, which shortened the median effective treatment duration by 14 days but required 3 fewer doses.
UNASSIGNED: These simulated results, when combined with the favorable observational data, support the use of commonly reported dalbavancin regimens for prolonged therapy durations. In addition, these pharmacokinetic/pharmacodynamic data support extending the dosing interval beyond the frequently reported weekly regimens, which should be investigated further with a clinical trial.
摘要：
■Dalbavancin是一种长效脂糖肽抗生素，尽管缺乏食品和药物管理局对这些适应症的批准，但越来越多地用于需要延长治疗持续时间的感染。对于这些感染，达巴万星的最佳剂量尚无共识，也没有可用的药代动力学研究来确定长期使用的最佳剂量。
■进行了计算机药代动力学模拟，以评估常用给药方案产生的预测达巴万星浓度，除了改进的方案。评估的主要终点是在最小抑制浓度(AUC/MIC)>27.1(确立的PK目标)的曲线下中位24小时游离面积的天数。
■第0天和第7天的1500mg给药方案导致57天的中位数AUC/断点值高于目标值（较低的95％置信区间[CI]，37天）。在第0天和第21天的1500mg的修改方案导致另外11天的中值AUC/断点目标达成。建模的另一种标准给药方案是在第0天1000mg,然后每周500mg,用于5个剂量。该方案达到AUC/断点目标达76天(较低的95%CI,59天)。该方案在第0天修改为1000mg，然后在第14天和第28天修改为500mg，这将中位有效治疗持续时间缩短了14天，但需要减少3次剂量。
■这些模拟结果，结合有利的观测数据，支持使用常见报道的达巴万星方案延长治疗持续时间。此外,这些药代动力学/药效学数据支持将给药间隔延长到超过频繁报告的每周给药方案,应该通过临床试验进一步研究。
■进行了计算机药代动力学模拟，以评估常用给药方案产生的预测达巴万星浓度，除了改进的方案。评估的主要终点是在最小抑制浓度(AUC/MIC)>27.1(确立的PK目标)的曲线下中位24小时游离面积的天数。
■第0天和第7天的1500mg给药方案导致57天的中位数AUC/断点值高于目标值（较低的95％置信区间[CI]，37天）。在第0天和第21天的1500mg的修改方案导致另外11天的中值AUC/断点目标达成。建模的另一种标准给药方案是在第0天1000mg,然后每周500mg,用于5个剂量。该方案达到AUC/断点目标达76天(较低的95%CI,59天)。该方案在第0天修改为1000mg，然后在第14天和第28天修改为500mg，这将中位有效治疗持续时间缩短了14天，但需要减少3次剂量。
■这些模拟结果，结合有利的观测数据，支持使用常见报道的达巴万星方案延长治疗持续时间。此外,这些药代动力学/药效学数据支持将给药间隔延长到超过频繁报告的每周给药方案,应该通过临床试验进一步研究。
