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 met abolites (the erythro-alcohol, threo-alcohol, and N-desethyl metabolit es) in 27 subjects with various degrees of renal function after intrav enous 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 greater-than-or-e qual-to 75 ml . min-1 . 1.73 m-2; n = 13); group 2, moderate renal imp airment (creatinine clearance 30-60 ml . min-1 . 1.73 m-2; n = 8); gro up 3, severe renal impairment (creatinine clearance less-than-or-equal -to 30 ml . min-1 . 1.73 m-2; n = 6). The terminal half-life of batano pride was significantly prolonged from 2.7 h in group 1 to 9.9 h in gr oup 3. The renal clearance of batanopride was significantly lower in g roup 3 (25 ml . min-1) compared with group 1 (132 ml . min-1).There we re 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 co mpared with group 1. The half-lives of all three metabolites were sign ificantly prolonged in group 3 compared with group 1. The dose of bata nopride may need to be reduced in patients with creatinine clearances less than 30 ml . min-1 . 1.73 m-2 to prevent drug accumulation and av oid possible dose-related adverse effects.