Bioavailability and disposition of metoclopramide after single- and multiple-dose administration in diabetic patients with gastroparesis.

The disposition of metoclopramide after acute and chronic administration was determined in four diabetic patients with gastroparesis who had a creatinine clearance of 70.8 +/- 10.7 mL/min (mean +/- SD). Single, 10-mg oral and intravenous doses were administered on days 1 and 2, respectively, followed by 10 mg orally every six hours for three weeks. A second, 10-mg intravenous bolus dose was administered on the last morning of chronic therapy. Metoclopramide concentrations were determined by high performance liquid chromatography. The elimination half-life, steady-state volume of distribution, and total body clearance after the initial intravenous dose were 3.9 +/- 1.2 hr, 2.7 +/- 0.3 L/kg, and 0.57 +/- 0.14 L/hr/kg, respectively. The initial bioavailability was 67.7 +/- 12.6%. After three weeks of chronic therapy, no significant differences in total body clearance (0.72 +/- 0.42 L/hr/kg) or bioavailability (77.5 +/- 16.8%) were observed. Thus the pharmacokinetics and bioavailability of metoclopramide were not altered during chronic therapy in these diabetic patients.