Optimizing Metoclopramide Control of Cisplatin-Induced Emesis

Abstract

Using an original high-pressure liquid chromatographic assay, we measured serum levels of metoclopramide and defined a concentration-response relationship for metoclopramide control of cisplatin-induced emesis. Using a metoclopramide regimen of 2 mg/kg body weight intravenously every 2 hours for four doses, we found that serum levels greater than 850 ng/mL immediately before the third dose were associated with complete control of emesis (less than three episodes) in 78% of patients and partial control (three to five episodes) in 18%. No patient with levels less than 850 ng/mL had complete control of emesis; only 42% had partial control (p < 0.001). Increases in dosage for patients with low levels and poor responses improved control in four of five patients. Elderly patients had drug levels similar to those of young patients but had fewer episodes of emesis (p = 0.044), suggesting that elderly patients have increased sensitivity to this drug. The metoclopramide dose can be raised up to 2.75 mg/kg with an improvement in emetic control in patients who have an inadequate response to doses of 2 mg/kg and no toxicity.