Metoclopramide kinetics at high-dose infusion rates for prevention of cisplatin-induced emesis

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Abstract
Eleven male subjects [with cancer] aged 24-58 yr received cisplatin, 90-120 mg/m2 i.v., in combination with other cytostatic drugs such as doxorubicin HCl and bleomycin. To prevent emesis, 2 high-dose metoclopramide regimens were started 2 h before cytostatic therapy. Regimen A (n = 7) consisted of a loading dose infusion of 1 mg/kg per h over 2 h, followed by a maintenance infusion of 0.5 mg/kg per h over 24 h (total dose was 14 mg/kg in each cytostatic cycle). Regimen B (n = 6) consisted of half the metoclopramide dose. The following kinetics were derived from the metoclopramide steady-state plasma levels and the t1/2 [half-time] of the elimination phase 26-38 h after dosing (median value and range are listed). Steady-state plasma concentration in group A and group B was 750 (480-1520) and 360 (300-480) ng/ml plasma. Drug clearance in group A and group B was 0.67 (0.3-7.0) and 0.70 (0.5-0.8) l/h per kg. Volumes of drug distribution in group A and group B were 4.4 (1.9-6.5) and 4.3 (3.2-5.9) l/kg. Values for the t1/2 in the elimination phase in group A and group B were 4.7 (3.0-5.4) and 4.3 (3.7-5.1) h. It appears that metoclopramide kinetics at high doses were dose linear, i.e., without evidence of cumulation. There were few side effects: vomiting was effectively suppressed by both regimes.

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