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Population Pharmacokinetics of Digoxin in Japanese Patients

A 2-Compartment Pharmacokinetic Model

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Abstract

Objective

To clarify the observed variability of digoxin disposition by performing a population pharmacokinetic analysis in a Japanese population.

Design

Retrospective analysis of clinical pharmacokinetic data.

Patients and participants

Data were obtained from 106 patients with heart failure and atrial fibrillation (43 males and 63 females).

Methods

Digoxin concentrations in serum were measured by fluorescence polarisation immunoassay. Population pharmacokinetic analysis was performed using a 2-compartment open pharmacokinetic model with the computer program NONMEM.

Results

246 serum concentrations were obtained. Final pharmacokinetic parameters were: CL (L/h) = (0.036 □TBW + 0.112 □CLCR) □0.77SPI □0.784CCB, V1 = 1.83 L/kg, V2 = 22.6 L/kg and Q = 0.629 L/h/kg, where CL is total body clearance, V1 and V2 are the apparent volumes of distribution in the central and peripheral compartments, Q is intercompartmental clearance, TBW is total bodyweight (in kg), CLCR is creatinine clearance (in ml/min), SPI = 1 for concomitant administration of spironolactone (and zero otherwise) and CCB = 1 for concomitant administration of calcium antagonists (and zero otherwise). Concomitant administration of digoxin and spironolactone resulted in a 23% decrease in digoxin clearance. Concomitant administration of digoxin and calcium antagonists (diltiazem, nicardipine, nifedipine or verapamil) resulted in a 21.6% decrease in digoxin clearance.

Conclusions

The estimated population parameter values may assist clinicians in the individualisation of digoxin dosage regimens.

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Acknowledgements

This study was supported by Grants-in-Aid from the Nakatomi Foundation and the Japan Research Foundation for Clinical Pharmacology.

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Authors and Affiliations

  1. Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Eiji Yukawa, Shigehiro Ohdo & Shun Higuchi

  2. Department of Hospital Pharmacy, Kyushu Kousei-Nenkin Hospital, Kitakyushu, Japan

    Fumihiro Suematu & Masao Minemoto

  3. Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    Miho Yukawa & Yoshinobu Goto

  4. Department of Hospital Pharmacy, Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan

    Toshinobu Aoyama

Authors
  1. Eiji Yukawa
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  2. Fumihiro Suematu
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  3. Miho Yukawa
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  4. Masao Minemoto
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  5. Shigehiro Ohdo
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  6. Shun Higuchi
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  7. Yoshinobu Goto
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  8. Toshinobu Aoyama
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Correspondence to Eiji Yukawa.

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Yukawa, E., Suematu, F., Yukawa, M. et al. Population Pharmacokinetics of Digoxin in Japanese Patients. Clin Pharmacokinet 40, 773–781 (2001). https://doi.org/10.2165/00003088-200140100-00005

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  • DOI: https://doi.org/10.2165/00003088-200140100-00005

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