Population pharmacokinetics of digoxin in japanese patients: A 2-compartment pharmacokinetic model

E. Yukawa, F. Suematu, M. Yukawa, M. Minemoto, Shigehiro Ohdo, S. Higuchi, Y. Goto, T. Aoyama

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
JournalClinical Pharmacokinetics
Volume40
Issue number10
DOIs
Publication statusPublished - Jan 1 2001

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Digoxin
varespladib methyl
Pharmacokinetics
Population
Spironolactone
Fluorescence Polarization Immunoassay
Calcium
Nicardipine
Diltiazem
Nifedipine
Verapamil
Serum
Atrial Fibrillation
Creatinine
Software
Heart Failure

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Population pharmacokinetics of digoxin in japanese patients : A 2-compartment pharmacokinetic model. / Yukawa, E.; Suematu, F.; Yukawa, M.; Minemoto, M.; Ohdo, Shigehiro; Higuchi, S.; Goto, Y.; Aoyama, T.

In: Clinical Pharmacokinetics, Vol. 40, No. 10, 01.01.2001, p. 773-781.

Research output: Contribution to journalArticle

Yukawa, E, Suematu, F, Yukawa, M, Minemoto, M, Ohdo, S, Higuchi, S, Goto, Y & Aoyama, T 2001, 'Population pharmacokinetics of digoxin in japanese patients: A 2-compartment pharmacokinetic model', Clinical Pharmacokinetics, vol. 40, no. 10, pp. 773-781. https://doi.org/10.2165/00003088-200140100-00005
Yukawa, E. ; Suematu, F. ; Yukawa, M. ; Minemoto, M. ; Ohdo, Shigehiro ; Higuchi, S. ; Goto, Y. ; Aoyama, T. / Population pharmacokinetics of digoxin in japanese patients : A 2-compartment pharmacokinetic model. In: Clinical Pharmacokinetics. 2001 ; Vol. 40, No. 10. pp. 773-781.
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AU - Yukawa, E.

AU - Suematu, F.

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AU - Minemoto, M.

AU - Ohdo, Shigehiro

AU - Higuchi, S.

AU - Goto, Y.

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N2 - 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.

AB - 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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