THE PHARMACOKINETICS OF REMOXIPRIDE AND METABOLITES IN PATIENTS WITH VARIOUS DEGREES OF RENAL-FUNCTION

1 The pharmacokinetics of remoxipride, a new neuroleptic, were investi gated in an open study with three parallel groups. Twenty-one patients with severely impaired (Cl(Cr) < 25 ml min-1), moderately impaired (C L(Cr) 25-50 ml min-1) and normal (Cl(Cr) > 65 ml min-1) renal function were evaluated. A single oral dose of remoxipride hydrochloride 100 m g was administered, and blood and urine were collected over 48 h. Conc entrations of remoxipride and metabolites were measured by h.p.l.c. 2 In patients with severely decreased renal function, the AUC and C(max) of remoxipride were increased significantly, and t1/2 was prolonged, as compared with the control patients. The renal clearance and urinary recovery of the unchanged drug were significantly diminished. 3 The u nbound fraction of remoxipride in plasma was decreased in patients wit h renal failure, in association with a disease-related increase in alp ha1-acid glycoprotein. In spite of a 25% recovery of unchanged drug in the urine in patients with normal renal function, the AUC of unbound drug was twice as high in patients with severely impaired renal functi on. 4 A strong correlation between creatinine clearance and renal drug clearance was observed indicating a direct relationship between kidne y function and the renal clearance of remoxipride. 5 Remoxipride was t he predominant compound in plasma as well as in urine in patients with severely decreased as well as normal renal function. In patients with severely decreased renal function, remoxipride and all five pharmacol ogically inactive metabolites showed increased peak plasma concentrati ons, delayed t(max), increased AUC, prolonged half-lives and decreased renal clearance.