The disposition and protein binding of batanopride and its metabolites in subjects with renal impairment.
We have studied the disposition of batanopride and its three major metabolites (the erythro-alcohol, threo-alcohol, and N-desethyl metabolites) in 27 subjects with various degrees of renal function after intravenous infusion of a single dose of 3.6.mg.kg-1 of batanopride over 15 min. The subjects were assigned to one of three treatment groups: group 1, normal renal function (creatinine clearance > or = 75 ml.min-1 x 1.73 m-2; n = 13); group 2, moderate renal impairment (creatine clearance 30-60 ml.min-1 x 1.73 m-2; n = 8); group 3, severe renal impairment (creatinine clearance < or = 30 ml.min-1 x 1.73 m-2; n = 6). The terminal half-life of batanopride was significantly prolonged from 2.7 h in group 1 to 9.9 h in group 3. The renal clearance of batanopride was significantly lower in group 3 (25 ml.min-1) compared with group 1 (132 ml.min-1). There were no differences in plasma protein binding or steady-state volume of distribution of batanopride among the groups. There were significantly lower renal clearances for all three metabolites in groups 2 and 3 compared with group 1. The half-lives of all three metabolites were significantly prolonged in group 3 compared with group 1. The dose of batanopride may need to be reduced in patients with creatinine clearances less than 30 ml.min-1 x 1.73 m-2 to prevent drug accumulation and avoid possible dose-related adverse effects.
St Peter
J V
JV
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.
Brady
M E
ME
Foote
E F
EF
Dandekar
K A
KA
Smaldone
L
L
Pykkonen
J L
JL
Keane
W F
WF
Halstenson
C E
CE
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008787:Metoclopramide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008875:Middle Aged; D011485:Protein Binding; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*
C083529:BMY 27267; C083528:BMY 33004; D001798:Blood Proteins; D012702:Serotonin Antagonists; C060190:batanopride; D008787:Metoclopramide