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Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

A Correction to this article was published on 16 September 2020

This article has been updated

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.

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Data availability

Data sharing not applicable to this study as no datasets were generated during current study. All data analyzed during this study are included in this published (the reference) articles.

Change history

  • 16 September 2020

    Figure 3 image was inadvertently removed from the original article. The original article has been corrected.

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 :

Rate constant from central compartment to peripheral compartment

k21 :

Rate constant from peripheral compartment to central compartment

ke :

Elimination rate constant

kG1 :

Transfer rate constant from GI1 compartment

kG2 :

Transfer rate constant from GI2 compartment to systemic compartment

tlag :

Lag time

tmax :

Time to reach maximum plasma concentration

Vd :

Volume of distribution

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Authors and Affiliations

  1. Division of Clinical Pharmacokinetics, Keio University Faculty of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8512, Japan

    Hisakazu Ohtani, Kota Nakamura, Ayuko Imaoka & Takeshi Akiyoshi

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  1. Hisakazu Ohtani
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  2. Kota Nakamura
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  3. Ayuko Imaoka
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  4. Takeshi Akiyoshi
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Contributions

Conceived of designed study: Ohtani, Imaoka, and Akiyoshi

Performed research/analyzed data: Ohtani, Nakamura, Imaoka, and Akiyoshi

Wrote the paper: Ohtani, Nakamura, Imaoka, and Akiyoshi

All authors read and approved the final manuscript.

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Correspondence to Hisakazu Ohtani.

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The original article was revised: Figure 3 image was inadvertently removed from the original article.

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Ohtani, H., Nakamura, K., Imaoka, A. et al. Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs. Eur J Clin Pharmacol 76, 1529–1536 (2020). https://doi.org/10.1007/s00228-020-02931-y

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