Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay.
OBJECTIVE
To determine digoxin pharmacokinetics in subjects with different degrees of renal function using fluorescence polarization immunoassay (FPIA), which is associated with less interference from digoxin-like immunoreactive substances (DLIS) than radioimmunoassay.


METHODS
University hospital clinical research center.


METHODS
Eighteen subjects (mean age 44 yrs) with different degrees of renal function: group 1, creatinine clearance (Clcr) below 10 ml/minute; group 2, Clcr 10-50 ml/minute; and group 3, Clcr greater than 50 ml/minute (6 patients in each group).


METHODS
Over 5-7 days, 15 serum samples were collected after a single intravenous dose of digoxin 7 or 10 micrograms/kg actual body weight (WT) for serum concentration measurements by FPIA. Two-compartment pharmacokinetic parameters (zero-time intercept of the concentration-time curve of the initial distribution phase [A], zero-time intercept of the concentration-time curve of the terminal elimination phase [B], initial distribution phase constant [alpha], terminal elimination rate constant [beta], volume of distribution in the central compartment [Vc] and at steady state [Vss], total body clearance [Cl], mean residence time [MRT], area under the concentration-time curve [AUC]) were determined using a nonlinear least squares regression program.


RESULTS
No significant differences were found among groups for A, B, alpha, beta, beta-half-life Vc/WT, MRT, AUC, and Cl/WT. Significant differences were observed in Vss/WT (4.8 +/- 1.0, 6.6 +/- 0.5, 6.4 +/- 0.7 L/kg) between group 1 versus group 2 and group 1 versus group 3 (p < 0.01). Measured Clcr was correlated with Cl (r2 = 0.40, p < 0.01), Cl/WT (r2 = 0.29, p < 0.05), Vss (r2 = 0.35, p = 0.01), and Vss/WT (r2 = 0.24, p < 0.05).


CONCLUSIONS
This study confirmed that Vss is smaller in patients with chronic renal failure (Clcr < 10 ml/min) than those without chronic renal failure. Therefore, previous recommendations that lower digoxin loading doses should be administered in patients with renal failure are applicable to digoxin serum concentration monitoring using FPIA.
Cheng
J W
JW
Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA.
Charland
S L
SL
Shaw
L M
LM
Kobrin
S
S
Goldfarb
S
S
Stanek
E J
EJ
Spinler
S A
SA
D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D004077:Digoxin; D003404:Creatinine; D011188:Potassium