Effect of haemodialysis on metoclopramide kinetics in patients with severe renal failure.

Abstract

The kinetics of metoclopramide and the effects of haemodialysis on metoclopramide kinetics were examined in eight uraemic subjects 1 h and 24 h prior to the onset of dialysis. In spite of the relatively minor contribution of renal clearance to total body clearance in normals, metoclopramide kinetics were substantially altered in uraemia. The total body clearance was decreased by 2-4 fold, terminal elimination half-life proportionately increased, while the volume of distribution appeared to be unaffected compared with that previously demonstrated in normal healthy subjects. Haemodialysis does not appear to be effective in removing metoclopramide from the body and metoclopramide clearance subsequent to dialysis is unaltered. The kinetic parameters in the uraemic subjects are not significantly different between drug administrations 1 or 24 h prior to the time of onset of haemodialysis. Following kidney transplantation, in one subject, there appeared to be a rapid return to apparently normal kinetics from the uraemic state.

Effects of serum from patients with chronic renal failure on rat hepatic cytochrome P450

“…Normalizing renal function with a kidney transplant completely reversed the inhibitory effects of serum on liver P450 compared to predialysis serum (Figure 6). Although no studies have been performed on liver P450 and renal transplantation, some authors have reported an increase in the metabolic clearance of drugs after successful kidney transplantation compared to dialysis (Wright et al ., 1988; Kim et al ., 1993). For instance, the nonrenal clearance of isoniazid and metoclopramide markedly increase following kidney transplantation compared to the clearance observed in hemodialysis (Wright et al ., 1988; Kim et al ., 1993).…”

Metoclopramide Therapy and Movement Disorders in a Diabetic–Uremic Subject With Bilateral Basal Ganglia Lesions

“…Thus, dopamine receptor antagonists may further impair striatal dopamine transmission and produce dopamine receptor hypersensitivity in the already-compromised basal ganglia of diabeticeuremic subjects. In addition, a significant proportion of the total body clearance of metoclopramide depends on adequate renal function, the half-life is markedly prolonged in chronic renal failure, 11 and the clearance of metoclopramide by CAPD is negligible because of its high molecular weight and large volume of distribution. 12 We speculated that metoclopramide therapy may further damage the vulnerable basal ganglia and lead to drug-induced parkinsonism and also the syndrome of acute bilateral basal ganglia lesions in this diabeticeuremic subject.…”

Pharmacokinetic Optimisation of Antiemetic Therapy

“…The CL of me to clop rami de in patients with renal impairment may be reduced by up to half (Bateman et al 1981;Wright et al 1988b); it is unaffected by haemodialysis, although anecdotal evidence suggests that the elimination rate returns to normal after transplantation (Wright et al 1988b). There are no published data on metoclopramide pharmacokinetics in liver disease, but I study suggested that very young children «1 month) may have impaired elimination of the drug (Kearns et al 1988).…”