Skip to main content
Log in

High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy.

Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations.

In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor.

There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophospamide and doxorubicin.

The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration.

Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allen JC, Reilly L, Gralla R, Kellick M (1983) Extrapyramidal reactions in children following high intravenous doses of metoclopramide, a new antiemetic. Ann Neurol 14: 369

    Google Scholar 

  • Bateman DN, Rawlins MD, Simpson J (1985) Extrapyramidal reactions with metoclopramide. Br Med J 291: 930–932

    Google Scholar 

  • 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

    Google Scholar 

  • Daniels M, Belt RJ (1982) High-dose metoclopramide as an antiemetic for patients receiving chemotherapy with cis-platinum. Oncol Nurs Forum 9: 20–22

    Google Scholar 

  • Edge S, Funkhouser W, Berman A, Seipp C, Tanner A, Wesley R, Rosenberg S, Chang A (1984) Randomised evaluation of high dose oral and intravenous metoclopramide in adriamycin/cytoxan induced emesis. Proc Am Soc Clin Oncol 3: 97

    Google Scholar 

  • Goslin RH, Garnick MB (1981) Metoclopramide as an antiemetic in patients receiving cisplatin. In: Poster D (ed) The treatment of nausea and vomiting induced by cancer chemotherapy. Masson, New York, p 159–164

    Google Scholar 

  • Gralla RJ, Itri LM, Pisko E, Squillante SE, Kelson DP, Braun DW, Bordin TJ, Young CW (1981) Antiemetic efficacy of high-dose metoclopramide: Randomised trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 305: 905–909

    Google Scholar 

  • Gralla RJ (1983) Metoclopramide. A review of anti-emetic trials. Drugs 25 [Suppl 1]: 63–73

    Google Scholar 

  • Homesley HD, Gainey JM, Jobson VW, Welander CE, Muss HB, Wells HB (1982) Metoclopramide as an antiemetic in chemotherapy. N Engl J Med 307: 250

    Google Scholar 

  • Joss RA, Galeazzi RL, Brunner KW (1983) Continuous infusion of high-dose metoclopramide for the prevention of nausea and vomiting in patients receiving cancer chemotherapy. Eur J Clin Pharmacol 25: 35–39

    Google Scholar 

  • 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 cis-platinum. Br J Clin Pharmacol 20: 426–427

    Google Scholar 

  • Kris MG, Gralla RJ, Tyson LB, Clark RA, Kelson DP, Reilly LK, Groshen S, Bosl GJ, Kalman LA (1985) Improved control of cisplatin-induced emesis with high-dose metoclopramide, dexamethasone and diphenhydramine. Cancer 55: 527–534

    Google Scholar 

  • Leyland-Jones B, Gralla RJ, Pitts J, Williams L, Young CW, Wright G (1984) Non-saturable kinetics of high dose metoclopramide. Clin Pharmacol Ther 35: 256

    Google Scholar 

  • McDermed JE, Cohen JL, Joseph C, Strum SB (1985) Clinical pharmacokinetics of high-dose metoclopramide in cancer patients receiving cisplatin therapy. J Clin Oncol 3: 1400–1408

    Google Scholar 

  • Meyer BR, Lewin M, Drayer ODE, Pasmantier M, Lonski L, Reidenberg MM (1984) Optimizing metoclopramide control of cisplatin-induced emesis. Ann Int Med 100: 393–395

    Google Scholar 

  • Nelder JA, Wedderburn RWM (1972) Generalized linear models. J R Stat Soc Series A 135: 70–84

    Google Scholar 

  • Prescent CA, Wiseman C, Gala K, Kennedy P, Bouzaglou A, Schindler J, Rigas M, Melville J, Dolan J (1986) Antiemetic effects of metoclopramide continuous infusion: safety, efficacy, patient preference and cost reduction. Proc Am Soc Clin Oncol 5: 254

    Google Scholar 

  • Roemeling RV, Christiansen NP, Hrushesky WJM (1985) Lack of antiemetic effect of high-dose metoclopramide. J Clin Oncol 3: 1273–1276

    Google Scholar 

  • Roila F, Tonato M, Basurto C, Canaletti R, Morsia D, Passalacqua R, Di Costanzo F, Donati D, Colombo N, Ballatori E, Del Favero A, Tognoni G, Franzosi MG (1985) Antiemetic activity of two different high doses of metoclopramide in cisplatin-treated cancer patients: A randomized double-blind trial of the Italian oncology group for clinical research. Cancer Treat Rep 69: 1353–1357

    Google Scholar 

  • 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

    Google Scholar 

  • Taylor WB, Proctor SJ, Bateman DN (1984) Pharmacokinetics and efficacy at high-dose metoclopramide given by continuous infusion for the control of cytotoxic drug-induced vomiting. Br J Clin Pharmacol 18: 679–684

    Google Scholar 

  • Taylor WB, Bateman DN (1986) Oral bioavailability of high-dose metoclopramide. Eur J Clin Pharmacol 31: 41–44

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, W.B., Simpson, J.M. & Bateman, D.N. High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy. Eur J Clin Pharmacol 33, 161–165 (1987). https://doi.org/10.1007/BF00544561

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00544561

Key words

Navigation