Summary
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 · 1−1, close to that aimed for (1.20 mg · 1−1). It was significantly different from that in the other group, v0.54 mg · 1−1. Antiemetic efficacy, defined as ⩽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.
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References
Gralla RJ, Itri LM, Pisko SE, Squillante AE, Kelsen DP, Braun DW, Bordin LA, Braun TJ, Young CW (1981) Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 305: 905–909
Gralla RJ (1983) Metoclopramide. A review of antiemetic trials. Drugs 25 [Suppl 1]: 63–73
Kris MG, Gralla RJ, Tyson LB, Clark RA, Kelsen DP, Reilly LK, Groshen S, Bosl GJ, Kalman LA (1985) Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients. Cancer 55: 527–534
Kerr DJ, Graham J, Blackie RG, McGovern E, Kelman AW, Cunningham D, Kaye SB (1985) The relationship between steady state metoclopramide levels and control of emesis during treatment with cisplatinum. Br J Clin Pharmacol 20: 426–427
Warrington PS, Allan SG, Cornbleet MA, Macpherson JS, Smyth JF, Leonard RCF (1986) Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high-dose metoclopramide in emesis induced by cisplatin. Br Med J 293: 1334–1337
McGovern EM, Grevel J, Bryson SM (1986) Pharmacokinetics of high-dose metoclopramide in cancer patients. Clin Pharmacokinet 11: 415–424
Brechot JM, Dupeyron JP, Guyon F, Delfour C, Delattre C, Lebeau B, Rochemaure J (1988) Ajustement posologique du métoclopramide pour le contrôle des vomissements induits par le cisplatine: approche pharmacocinétique. Presse Med 17: 1147–1149
Bryson SM, McGovern EM, Kelman AW, White K, Addis GJ, Whiting B (1985) The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease. Br J Clin Pharmacol 19: 757–766
Guyon F, Delfour C, Delattre C, Dupeyron JP (1987) Liquidchromatographic assay of metoclopramide in human plasma. Clin Chem 33: 190–191
Miller LC, Tainter ML (1944) Estimation of the EDSO and its error by means of logarithmic probit graph paper. Proc Soc Exp Biol Med 57: 261–264
Meyer BR, Lewin M, Drayer DE, Pasmantier M, Lonski L, Reindenberg MM (1984) Optimizing metoclopramide control of cisplatin-induced emesis. Ann Intern Med 100: 393–395
Saller R, Hellenbrecht D, Briemann L, Hellstern A, Hess H, Mitrou P, Hodgson M, Achtert G, Brockmann P, Hausleiter HJ (1985) Metoclopramide kinetics at high-dose infusion rates for prevention of cisplatin-induced emesis. Clin Pharmacol Ther 37: 43–47
Saller R, Hellenbrecht D, Hellstern A, Hess H (1985) Improved benefit/risk ratio of higher-dose metoclopramide therapy during cisplatin-induced emesis. Eur J Clin Pharmacol 29: 311–312
Taylor WB, Simpson JM, Bateman DN (1987) High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationship in patients receiving cancer chemotherapy. Eur J Clin Pharmacol 33: 161–165
Olver IN, Simon RM, Aisner J (1986) Antiemetic studies: a methodological discussion. Cancer Treat Rep 70: 555–563
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Brechot, J.M., Dupeyron, J.P., Delattre, C. et al. Continuous infusion of high-dose metoclopramide: comparison of pharmacokinetically adjusted and standard doses for the control of cisplatin-induced acute emesis. Eur J Clin Pharmacol 40, 283–286 (1991). https://doi.org/10.1007/BF00315210
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DOI: https://doi.org/10.1007/BF00315210