Examination of the correlation of serum metoclopramide levels with antiemetic efficacy in patients receiving cisplatin

The existence of a threshold serum metoclopramide level above which total protection from cisplatin-induced vomiting is more likely to occur has been proposed. We monitored serum metoclopramide levels prior to the third metoclopramide dose in the first cisplatin treatment cycle in patients receiving metoclopramide 2 mg/kg x 4 as part of a randomized double-blind cross-over study comparing single-agent metoclopramide with combination metoclopramide and dexamethasone. Serum samples from 35 patients (17 receiving single-agent metoclopramide and 18 receiving the combination) were analyzed using reverse-phase high-pressure liquid chromatography (HPLC). A wide variation in metoclopramide levels was observed (range 273-3380 ng/ml). Serum levels obtained from the same patient on multiple treatment cycles were well correlated, and the addition of dexamethasone did not alter serum metoclopramide levels. No threshold level could be identified for the two groups (single-agent or combination antiemetic therapy) considered individually or considered together. However, significantly more vomiting episodes and a lower incidence of total protection were noted in patients with metoclopramide levels above 1469 ng/ml receiving metoclopramide alone. This effect was nullified in the combination antiemetic group. Our data do not support a directly proportional relationship between serum metoclopramide level and antiemetic protection. However, a non-linear relationship with a possible agonist/antagonist effect is suggested.