Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs
- PDF / 364,060 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 83 Downloads / 153 Views
PHARMACOKINETICS AND DISPOSITION
Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs Hisakazu Ohtani 1
&
Kota Nakamura 1 & Ayuko Imaoka 1 & Takeshi Akiyoshi 1
Received: 2 March 2020 / Accepted: 5 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Drug interaction . Charcoal . Pharmacokinetic model . Gastrointestinal absorption
Abbreviations AIC Akaike’s information criterion AUC Area under the plasma concentration-time curve AUCR AUC ratio (the ratio of AUC in the presence of activated charcoal to that in the absence of activated charcoal) AUCRobs Observed AUCR AUCRe Estimated AUCR D Dose DDI Drug-drug interaction
k12 k21 ke kG1 kG2 tlag tmax Vd
Rate constant from central compartment to peripheral compartment Rate constant from peripheral compartment to central compartment Elimination rate constant Transfer rate constant from GI1 compartment Transfer rate constant from GI2 compartment to systemic compartment Lag time Time to reach maximum plasma concentration Volume of distribution
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-02931-y) contains supplementary material, which is available to authorized users.
Introduction * Hisakazu Ohtani [email protected] 1
Division of Clinical Pharmacokinetics, Keio University Faculty of Pharmacy, 1-5-30, Shibakoen, Minato-k
Data Loading...
