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Title: Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs. Author: Ohtani H, Nakamura K, Imaoka A, Akiyoshi T. Journal: Eur J Clin Pharmacol; 2020 Nov; 76(11):1529-1536. PubMed ID: 32556909. Abstract: PURPOSE: Activated charcoal is known to adsorb a variety of drugs concomitantly administered and reduce their intestinal absorption, and separating the dosing is considered a practical approach to avoid this drug interaction. The aim of the present study was to develop and validate a simple method to estimate the sufficient dosing interval to avoid drug interaction using the pharmacokinetic profile of the subject drugs administered alone and the amplitude of interaction upon simultaneous administration with activated charcoal. METHODS: For each subject drug, the pharmacokinetic profile and the amplitude of interaction, as assessed by AUCR (the ratio of area under the plasma concentration-time curve (AUC) in the presence of activated charcoal to that in its absence), were collected from previous reports. The AUCR value was estimated based on the compartment model under the assumption that the subject drug in the first gastrointestinal compartment is immediately adsorbed to a certain extent upon the administration of activated charcoal. The estimated AUCR (AUCRe) for each drug with certain dosing interval was compared with the respective AUCR value reported previously (AUCRobs). RESULTS: Among twenty concentration profiles for 14 subject drugs obtained from previous reports, 15 AUCRe values fell in the range of 80-120% of the respective AUCRobs values. CONCLUSION: The developed method enabled estimation of the amplitude of DDI by activated charcoal administered in a certain dosing interval, whereas overestimation of AUCRe was observed for drugs that undergo extensive enterohepatic circulation.[Abstract] [Full Text] [Related] [New Search]