Carral Nerea, Lukas John C, Estradé Oskar, Jauregizar Nerea, Morillas Héctor, Suárez Elena
Department of Pharmacology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, Spain.
Drug Modeling & Consulting, Dynakin SL, 48160 Derio, Spain.
Antibiotics (Basel). 2023 May 1;12(5):838. doi: 10.3390/antibiotics12050838.
The consequences of non-adherence to treatment (NAT) on antimicrobial efficacy may depend on drug forgiveness-a property that should account for pharmacokinetics (PK) and pharmacodynamics (PD) as well as interindividual variability. In this simulation study, relative forgiveness (RF) in NAT, defined as the probability of a successful PK/PD target (PTA) attained under perfect adherence compared to imperfect adherence, was evaluated for amoxicillin (AMOX) (oral 1000 mg/8 h) and two respiratory fluoroquinolones-levofloxacin (LFX) (oral 750 mg/24 h) and moxifloxacin (MOX) (oral 400 mg/24 h)-in virtual outpatients with community-acquired pneumonia for . Several NAT scenarios (delay in dose intake and a missed dose) were considered. PK characteristics of virtual patients, including variability in creatinine clearance (70-131 mL/min) and susceptibility variability associated with geographical location, were simulated in NAT. In this regard, in regions of low MIC delays from 1 h to 7 h or omission of dose ingestion would not have negative consequences on the efficacy of AMOX because of its good RF associated with the AMOX PK and PD properties; RF of LFX 750 mg or MOX 400 mg/24 h regimen vs. AMOX 1000 mg/8 h is one. However, in regions of elevated MIC for AMOX loses its RF, LFX and MOX vs. AMOX, showing higher RF (>1) depending on the CL of patients. These results illustrate the importance of considering the RF of antimicrobial drugs in NAT and provide a framework for further studying its implications for clinical success rates.
不坚持治疗（NAT）对抗菌疗效的影响可能取决于药物宽容度——这一特性应考虑药代动力学（PK）和药效动力学（PD）以及个体间差异。在这项模拟研究中，评估了NAT中的相对宽容度（RF），其定义为与不完全依从相比，完全依从时达到成功PK/PD目标（PTA）的概率，研究对象为患有社区获得性肺炎的虚拟门诊患者使用阿莫西林（AMOX）（口服1000 mg/8小时）以及两种呼吸喹诺酮类药物——左氧氟沙星（LFX）（口服750 mg/24小时）和莫西沙星（MOX）（口服400 mg/24小时）的情况。考虑了几种NAT场景（剂量摄入延迟和漏服一剂）。在NAT中模拟了虚拟患者的PK特征，包括肌酐清除率的变异性（70 - 131 mL/分钟）以及与地理位置相关的药敏变异性。在这方面，在低MIC区域，AMOX从1小时到7小时的剂量延迟或漏服不会对其疗效产生负面影响，因为其与AMOX的PK和PD特性相关的良好RF；LFX 750 mg或MOX 400 mg/24小时方案与AMOX 1000 mg/8小时方案相比的RF为1。然而，在AMOX的MIC升高区域，AMOX失去其RF，LFX和MOX与AMOX相比，根据患者的CL显示出更高的RF（>1）。这些结果说明了在NAT中考虑抗菌药物RF的重要性，并为进一步研究其对临床成功率的影响提供了一个框架。
