Erythrocyte Na+, K+-ATPase and serum digoxin concentrations

A. H L From, G. J. Quarfoth, Bernard W Steele, K. Ahmed

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between "therapeutic" and "toxic" serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na+, K+-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na+, K+-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na+, K+-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na+,K+-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na+,K+-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.

Original languageEnglish
Pages (from-to)807-812
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Volume24
Issue number6
DOIs
StatePublished - Nov 1 1983
Externally publishedYes

Fingerprint

Digoxin
Erythrocytes
Serum
sodium-translocating ATPase
Poisons
Feasibility Studies
Therapeutics
Membranes

Keywords

  • chronic digoxin therapy
  • digoxin-receptor interaction
  • erythrocyte ghosts
  • Na,K-ATPase inhibition
  • serum digoxin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Erythrocyte Na+, K+-ATPase and serum digoxin concentrations. / From, A. H L; Quarfoth, G. J.; Steele, Bernard W; Ahmed, K.

In: European Journal of Clinical Pharmacology, Vol. 24, No. 6, 01.11.1983, p. 807-812.

Research output: Contribution to journalArticle

From, A. H L ; Quarfoth, G. J. ; Steele, Bernard W ; Ahmed, K. / Erythrocyte Na+, K+-ATPase and serum digoxin concentrations. In: European Journal of Clinical Pharmacology. 1983 ; Vol. 24, No. 6. pp. 807-812.
@article{e2f2c7365f7f4a159ec775eec9306e6c,
title = "Erythrocyte Na+, K+-ATPase and serum digoxin concentrations",
abstract = "Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between {"}therapeutic{"} and {"}toxic{"} serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na+, K+-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na+, K+-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na+, K+-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na+,K+-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na+,K+-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.",
keywords = "chronic digoxin therapy, digoxin-receptor interaction, erythrocyte ghosts, Na,K-ATPase inhibition, serum digoxin",
author = "From, {A. H L} and Quarfoth, {G. J.} and Steele, {Bernard W} and K. Ahmed",
year = "1983",
month = "11",
day = "1",
doi = "10.1007/BF00607092",
language = "English",
volume = "24",
pages = "807--812",
journal = "European Journal of Clinical Pharmacology",
issn = "0031-6970",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Erythrocyte Na+, K+-ATPase and serum digoxin concentrations

AU - From, A. H L

AU - Quarfoth, G. J.

AU - Steele, Bernard W

AU - Ahmed, K.

PY - 1983/11/1

Y1 - 1983/11/1

N2 - Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between "therapeutic" and "toxic" serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na+, K+-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na+, K+-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na+, K+-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na+,K+-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na+,K+-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.

AB - Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between "therapeutic" and "toxic" serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na+, K+-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na+, K+-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na+, K+-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na+,K+-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na+,K+-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.

KW - chronic digoxin therapy

KW - digoxin-receptor interaction

KW - erythrocyte ghosts

KW - Na,K-ATPase inhibition

KW - serum digoxin

UR - http://www.scopus.com/inward/record.url?scp=0020577360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020577360&partnerID=8YFLogxK

U2 - 10.1007/BF00607092

DO - 10.1007/BF00607092

M3 - Article

C2 - 6309531

AN - SCOPUS:0020577360

VL - 24

SP - 807

EP - 812

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 6

ER -