Continuous infusion of high-dose metoclopramide: comparison of pharmacokinetically adjusted and standard doses for the control of cisplatin-induced acute emesis.
Metoclopramide was administered by continuous infusion to two groups each of 14 patients on chemotherapy, randomized to receive either doses adjusted to individual pharmacokinetic parameters or doses adjusted as usual to body weight. The mean plasma concentration at the end of the infusion in the adjusted group was 1.01 mg.l-1, close to that aimed for (1.20 mg.l-1). It was significantly different from that in the other group. v 0.54 mg.l-1. Antiemetic efficacy, defined as less than or equal to 2 emetic events in the 24 h following cisplatin, was similar in both groups (being found in 12/14 (86%) and 10/14 patients (71%), respectively). Analysis of the cumulative percentage of responders according to plasma concentration showed a clear plasma concentration-effect relationship. Routine MCP pharmacokinetic dosage adjustment is not indicated, but this therapeutic approach can be used to optimize antiemetic therapy in poor responder patients.
Brechot
J M
JM
Department of Respiratory Medicine, Hotel Dieu, Paris, France.
Dupeyron
J P
JP
Delattre
C
C
Chastang
C
C
Laaban
J P
JP
Rochemaure
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002945:Cisplatin / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008787:Metoclopramide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D008787:Metoclopramide; D002945:Cisplatin