IS THE VOLUME OF DISTRIBUTION OF DIGOXIN REDUCED IN PATIENTS WITH RENAL DYSFUNCTION - DETERMINING DIGOXIN PHARMACOKINETICS BY FLUORESCENCE POLARIZATION IMMUNOASSAY

Study Objective. To determine digoxin pharmacokinetics in subjects wit h different degrees of renal function using fluorescence polarization immunoassay (FPIA), which is associated with less interference from di goxin-like immunoreactive substances (DLIS) than radioimmunoassay. Set ting. University hospital clinical research center. Participants. Eigh teen subjects (mean age 44 yrs) with different degrees of renal functi on: group 1, creatinine clearance (Cl-cr) below 10 ml/minute; group 2, Cl-cr 10-50 ml/minute; and group 3, Cl-cr greater than SO ml/minute ( 6 patients in each group). Intervention. Over 5-7 days, 15 serum sampl es were collected after a single intravenous dose of digoxin 7 or 10 m u g/kg actual body weight (WT) for serum concentration measurements by FPIA. Two-compartment pharmacokinetic parameters (zero-rime intercept of the concentration-time curve of the initial distribution phase [A] , zero-lime intercept of the concentration-lime curve of the terminal elimination phase [B], initial distribution phase constant [alpha], te rminal elimination rate constant [beta], volume of distribution in the central compartment [V-c] and at steady slate [V-c], total body clear ance [Cl], mean residence time [MRT], area under the concentration-rim e curve [AUC]) were determined using a nonlinear least squares regress ion program. Measurements and Main Results. No significant differences were found among groups for A, B, alpha, beta, beta-half-life, V-c/WT , MRT, AUG, and Cl/WT. Significant differences were observed in V-ss/W T (4.8 +/- 1.0, 6.6 +/- 0.5, 6.4 +/- 0.7 L/kg) between group I versus group 2 and group 1 versus group 3 (p<0.01). Measured Cl-cr was correl ated with Cl (r(2)=0.40, p<0.01), Cl/WT (r(2)=0.29, p<0.05), V-ss (r(2 )=0.35, p=0.01), and V-ss/WT (r(2)=0.24, p<0.05). Conclusion. This stu dy confirmed that V-ss is smaller in patients with chronic renal failu re (Cl-cr < 10 ml/min) than those without chronic renal failure. There fore, previous recommendations that lower digoxin loading doses should be administered in patients with renal failure are applicable to digo xin serum concentration monitoring using FPIA.