Simulation of optimal dose regimens of photoactivated curcumin for antimicrobial resistance pneumonia in COVID-19 patients:A modeling approach  

作　　者：Teerachat Saeheng Kesara Na-Bangchang 

机构地区：[1]Centre of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma,Chulabhorn International College,99 Moo 18,Phaholyothin Road,Thammasat University(Rangsit Campus),Klongneung,Klongluang District,Pathumthani,12121,Thailand [2]Drug Discovery and Development Centre,Office of Advanced Science and Technology,99 Moo 18,Phaholyothin Road,Thammasat University(Rangsit Campus),Klongneung,Klongluang,Pathumthani,12121,Thailand

出　　处：《Infectious Disease Modelling》2023年第3期783-793,共11页传染病建模（英文）

基　　金：supported by postdoctoral fellowship,Thammasat University(Rangsit Campus),Thailand;Kesara Na-Bangchang was received funding from Thammasat University under the project Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma(No.1/2556,dated October 12,2013);the National Research Council of Thailand(No.45/2561,dated September 10,2018);Kesara Na-Bangchang is supported by the National Research Council of Thailand under the Research Team Promotion grant(grant number NRCT 820/2563,dated November 12,2020).

摘　　要：Background:Secondary antimicrobial resistance bacterial(AMR)pneumonia could lead to an increase in mortality in COVID-19 patients,particularly of geriatric patients with underlying diseases.The comedication of current medicines for AMR pneumonia with corticosteroids may lead to suboptimal treatment or toxicities due to drug-drug interactions(DDIs).Objective:This study aimed to propose new promising dosage regimens of photoactivated curcumin when co-administered with corticosteroids for the treatment of antimicrobial resistance(AMR)pneumonia in COVID-19 patients.Methods:A whole-body physiologically-based pharmacokinetic(PBPK)with the simplified lung compartments model was built and verified following standard model verification(absolute average-folding error or AAFEs).The pharmacokinetic properties of photo-activated were assumed to be similar to curcumin due to minor changes in physiochemical properties of compound by photoactivation.The acceptable AAFEs values were within 2-fold.The verified model was used to simulate new regimens for different formulations of photoactivated curcumin.Results:The AAFEs was 1.12-fold.Original formulation(120 mg once-daily dose)or new intramuscular nano-formulation(100 mg with a release rate of 10/h given every 7 days)is suitable for outpatients with MRSA pneumonia to improve patient adherence.New intravenous formulation(2000 mg twice-daily doses)is for hospitalized patients with both MRSA and VRSA pneumonia.Conclusion:The PBPK models,in conjunction with MIC and applied physiological changes in COVID-19 patients,is a potential tool to predict optimal dosage regimens of photo-activated curcumin for the treatment of co-infected AMR pneumonia in COVID-19 patients.Each formulation is appropriate for different patient conditions and pathogens.

关 键 词：PBPK MRSA VRSA Photoactivated-curcumin COVID-19 PNEUMONIA Antimicrobial-resistance bacteria Pharmacokinetics 

分 类 号：R563.1[医药卫生—呼吸系统] R511[医药卫生—内科学]