Abstract：
BACKGROUND: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice.
METHODS: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light.
RESULTS: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same.
CONCLUSIONS: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed.
METHODS: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light.
RESULTS: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same.
CONCLUSIONS: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed.
摘要：
背景：使用氨基酮戊酸（ALA）的抗微生物光动力疗法（aPDT）是抗生素疗法的有希望的替代方案。ALA给药诱导原卟啉IX（PpIX）在细菌中的积累，并且累积的PpIX的光激发产生对细菌毒性的单线态氧。几个因素,包括药物管理和光照条件，有助于抗生素的效果。对于临床实践中的有效aPDT，应适度确定此类多个参数。
方法：构建了预测ALA-aPDT在临床条件下的细菌动力学的数学模型。应用药代动力学（PK-PD）方法，广泛用于抗菌药物评估，通过将杀菌率定义为当光照射细菌中的PpIX时产生的单线态氧的浓度来计数活细菌。
结果：ALA-aPDT对铜绿假单胞菌的体外实验结果证明了PK-PD模型的有效性。杀伤率是有上限的,当光剂量相同时，较低的功率密度长照射时间可以抑制活菌数。
结论：本研究提出了基于PK-PD模型的ALA-aPDT细菌生存力变化模型，通过使用PA的体外实验，可以表达细菌活力随光敏物质浓度和光照功率密度的变化。将需要用其他革兰氏阴性和革兰氏阳性菌株进一步验证PK-PD模型。
方法：构建了预测ALA-aPDT在临床条件下的细菌动力学的数学模型。应用药代动力学（PK-PD）方法，广泛用于抗菌药物评估，通过将杀菌率定义为当光照射细菌中的PpIX时产生的单线态氧的浓度来计数活细菌。
结果：ALA-aPDT对铜绿假单胞菌的体外实验结果证明了PK-PD模型的有效性。杀伤率是有上限的,当光剂量相同时，较低的功率密度长照射时间可以抑制活菌数。
结论：本研究提出了基于PK-PD模型的ALA-aPDT细菌生存力变化模型，通过使用PA的体外实验，可以表达细菌活力随光敏物质浓度和光照功率密度的变化。将需要用其他革兰氏阴性和革兰氏阳性菌株进一步验证PK-PD模型。
