The effect of age on digoxin pharmacokinetics in Fischer-344 rats

Journal Article · Mon Jan 01 00:00:00 EST 1990 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(90)90083-7· OSTI ID:7244648

Evans, R L; Owens, S M; Ruch, S; Kennedy, R H; Seifen, E ^[1]

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1. Univ. of Arkansas for Medical Sciences, Little Rock (USA)

Digoxin protein binding and pharmacokinetics were studied in 4-, 14-, and 25-month-old male Fischer-344 rats to determine if there were age-dependent changes in digoxin disposition. Serum protein binding did not differ among age groups. The average percentage unbound digoxin for all animals was 61.3 {plus minus} 5.3% (means {plus minus} SD, n = 15). For pharmacokinetic studies, ({sup 3}H)digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group. The ({sup 3}H)digoxin terminal elimination half-life was 2.0, 2.3, and 2.5 hr, respectively. The steady-state volume of distribution in the three age groups was 1.51, 1.49, and 1.27 liters/kg, respectively. Total body clearance for the three age groups was 14.2, 12.1, and 7.5 ml/min/kg, respectively. Analysis of variance of these data followed by Duncan's multiple range test indicated a significant decrease in clearance in the aged rats (25-month-old, p less than 0.05). This age-dependent decrease in clearance suggested that digoxin pharmacokinetics could be a significant factor in age-related alterations in digoxin cardiotoxicity in the rat, as it is in humans, and that the Fischer-344 rat could be a useful model for studies of digoxin pharmacokinetic changes with age.

• OSTI ID: 7244648
• Journal Information: Toxicology and Applied Pharmacology; (USA), Vol. 102:1; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DIGOXIN
BIOCHEMICAL REACTION KINETICS
AGE DEPENDENCE
BIOLOGICAL HALF-LIFE
CLEARANCE
INTRAVENOUS INJECTION
LIQUID COLUMN CHROMATOGRAPHY
RATS
STEADY-STATE CONDITIONS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHROMATOGRAPHY
DIGITALIS GLYCOSIDES
DRUGS
GLYCOSIDES
HYDROGEN COMPOUNDS
INJECTION
INTAKE
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
ORGANIC COMPOUNDS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques