Effect of renal function on risedronate pharmacokinetics after a single oral dose.
OBJECTIVE
To determine the relationship between risedronate pharmacokinetics and renal function.


METHODS
Risedronate was administered to adult men and women (n=21) with various degrees of renal function (creatinine clearance 15-126 ml min-1 ) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression.


RESULTS
Renal clearance and volume of distribution were linearly related to creatinine clearance (r2=0.854, P<0.001; and r2=0.317, P<0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min-1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min-1 (P=0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population.


CONCLUSIONS
Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance >20 ml min-1 ).
Mitchell
D Y
DY
Procter & Gamble Pharmaceuticals, Cincinnati, OH, USA.
St Peter
J V
JV
Eusebio
R A
RA
Pallone
K A
KA
Kelly
S C
SC
Russell
D A
DA
Nesbitt
J D
JD
Thompson
G A
GA
Powell
J H
JH
D000284:Administration, Oral; D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics*; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D000068296:Risedronic Acid
D002121:Calcium Channel Blockers; D000068296:Risedronic Acid; D012968:Etidronic Acid