Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis

The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851 +/- 361 ng/ml in group A versus 840 +/- 348 ng/ml in group B; after the 5th infusion it was 2,005 +/- 588 ng/ml in group A versus 2,463 +/- 1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582 +/- 308 ng/ml in group A versus 379 +/- 170 ng/ml in group B; P less than 0.05) and in the elimination half life (8.5 +/- 2.6 h in group A versus 6.1 +/- 1.1 h in group B; P less than 0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.