Background: Photoactivated curcumin primarily exerts its
therapeutic effects through the light-induced generation of reactive oxygen
species (ROS), resulting in oxidative stress, mitochondrial apoptosis, and
modulation of inflammatory pathways. This study aimed to develop whole-body
physiologically based pharmacokinetic (PBPK) models to identify appropriate
dosing regimens of photoactivated curcumin as an antimicrobial treatment for
bacterial-resistant infections.
Methods: A whole-body physiologically based pharmacokinetic (PBPK)
model was constructed using in vitro and human physiological parameters and
validated against a clinical study of curcumin at oral doses of 4000, 6000, and
8000 mg. The verified model was used to simulate novel dosing strategies for
photoactivated curcumin formulations. The rate of absorption and
water-solubility properties influenced the once-daily and twice-daily oral
dosing regimens of photoactivated curcumin. Considering long-acting
intramuscular dosing, a weekly dose of 1500 mg with a first-order release rate
from the intramuscular depot (Kim) of 0.012 /h and a weekly dose of 1250 mg
with the Kim of 0.015 resulted in sufficient exposure. A daily dose of 200 mg
with an infusion rate of 100 mg/h, twice-daily doses of 125 mg with an infusion
rate of 250 mg/h, and three times-daily doses of 100 mg with an infusion rate
of 200 mg/h provided satisfactory pharmacokinetic (PK) profiles.
Conclusion: PBPK modelling can be used as a tool to assist in dose
optimisation strategies of photoactivated curcumin in various clinical
conditions. The weekly intramuscular injection may improve compliance in
diseases that require long-term treatment, thereby reducing selective pressure
and drug resistance. The intravenous infusion could represent a suitable
strategy for critically ill patients in the hospital.
Author(s) Details
Teerachat Sae-heng
Chulabhorn International College of Medicine, Thammasat University, Rangsit
Center, 99 Moo 18, Phaholyothin Road, Klongneung Sub-District, Klong Luang
District, Pathumthani 12121, Thailand and Center of Excellence in Pharmacology
and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn
International College of Medicine, Rangsit Center, 99 Moo 18, Phaholyothin
Road, Klongneung Subdistrict, Klong Luang District, Pathumthani 12121,
Thailand.
Juntra Karbwang
Drug Discovery and Development Center, Office of Advanced Science and
Technology, Rangsit Center, Thammasat University, 99 Moo 18 Phaholyothin Road,
Klongneung Subdistrict, Klong Luang District, Pathumthani, 12121, Thailand.
Rajith Kumar Reddi Rajoli
Department of Pharmacology and Therapeutics, Center of Excellence in
Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, L69 3BX,
United Kingdom.
Marco Siccardi
Department of Pharmacology and Therapeutics, Center of Excellence in Long-acting
Therapeutics (CELT), University of Liverpool, Liverpool, L69 3BX, United
Kingdom.
Andrew Owen
Department of Pharmacology and Therapeutics, Center of Excellence in
Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, L69 3BX,
United Kingdom.
Kesara Na-Bangchang
Chulabhorn International College of Medicine, Thammasat University, Rangsit
Center, 99 Moo 18, Phaholyothin Road, Klongneung Sub-District, Klong Luang
District, Pathumthani 12121, Thailand, Center of Excellence in Pharmacology and
Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International
College of Medicine, Rangsit Center, 99 Moo 18, Phaholyothin Road, Klongneung
Subdistrict, Klong Luang District, Pathumthani 12121, Thailand and Drug
Discovery and Development Center, Office of Advanced Science and Technology,
Rangsit Center, Thammasat University, 99 Moo 18 Phaholyothin Road, Klongneung
Subdistrict, Klong Luang District, Pathumthani, 12121, Thailand.
Please see the book here:- https://doi.org/10.9734/bpi/psnid/v6/5797
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