Summary
Antiemetic drugs are used to treat nausea and vomiting due to a variety of causes and have a wide range of pharmacological properties. The choice of drug will, therefore, depend in part on the condition being treated. The drugs can be classified as dopamine antagonists (including phenothiazines and nonphenothiazines), corticosteroids, cannabinoids, benzodiazepines, serotonin antagonists, antihistamines and anticholinergics.
There is very little evidence of a relationship between plasma drug contentrations and either their efficacy or the incidence of adverse effects with most antiemetic drugs. With drugs for which concentration-effect studies have been performed, e.g. the benzodiazepines and antihistamines, the effects monitored have not been directly relevant to their use as antiemetics.
Antiemetics are used widely, for example, in cancer chemotherapy. Nonetheless, apart from metoclopramide, little work has been done on the influence of indicators of systemic disease on the pharmacokinetics of antiemetic drugs.
Similar content being viewed by others
References
Al-Habet SMH, Rogers HJ. Methylprednisolone pharmacokinetics after intravenous and oral administration. British Journal of Clinical Pharmacology 27: 285–290, 1989
Antal EJ, Wright III CE, Gillespie WR, Albert KS. Influence of the route of administration on the pharmacokinetics of methylprednisolone. Journal of Pharmacokinetics and Biopharmaceutics 11: 561–576, 1983
Aronson JK, Sear JW. Transdermal hyoscine (scopolamine) and postoperative vomiting. Anaesthesia 41: 1–3, 1986
Bass NM, Williams RL. Guide to drug dosage in hepatic disease. In Mammen GJ (Ed.) Clinical Pharmacokinetics drug data handbook, ADIS Press, Auckland, 1990
Bateman DN, Kahn C, Davies DS. Concentration effect studies with metoclopramide. British Journal of Clinical Pharmacology 8: 179–182, 1979
Bateman DN, Gokal R, Dodd TRP, Blain PG. The pharmacokinetics of single doses of metoclopramide in renal failure. European Journal of Clinical Pharmacology 19: 437–441, 1981
Bateman DN. Clinical pharmacokinetics of metoclopramide. Clinical Pharmacokinetics 8: 523–529, 1983
Bateman DN, Craft AW, Nicholson E, Pearson ADJ. Dystonic reaction and the pharmacokinetics of metoclopramide in children. British Journal of Clinical Pharmacology 15: 560–563, 1983
Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom. Quarterly Journal of Medicine, New Series 59: 549–556, 1986
Beckett AH, Berendt WA, Hadzija BW. Bioavailability of controlled-release metoclopramide. Arzeimittel-Forschung (Drug Research) 37: 221–224, 1987
Begg EJ, Atkinson HC, Gianarakis N. The pharmacokinetics of corticosteroid agents. Medical Journal of Australia 146: 37–41, 1987
Bennett WM. Guide to drug dosage in renal failure. In Mammen GJ (Ed.) Clinical Pharmacokinetics drug data handbook, ADIS Press, Auckland, 1990
Bilzer W, Gunert-Remy U, Weber E. Relationship between antihistaminic activity and plasma level of diphenhydramine. European Journal of Clinical Pharmacology 7: 393–395, 1974
Block W, Pingoud A, Khan M, Kjellerup P. The pharmacokinetics, bioequivalence and bioavailability of different formulations of metoclopramide. Arzeimittel-Forschung 31: 1041–1045, 1981
Brady ME, Sartiano GP, Rosenblum SL, Zaglama NE, Bauguess CT. The pharmacokinetics of single high doses of dexamethasone in cancer patients. European Journal of Clinical Pharmacology 32: 593–596, 1987
Brogden RN, Carmine AA, Heel RC. Domperidone: a review of its pharmacologic activity, pharmacokinetics and therapeutic efficacy in the treatment of chronic dyspepsia and as an antiemetic. Drugs 24: 360–400, 1982
Carruthers SG, Shoeman DW, Hignite CE, Azarnoff DL. Correlation between plasma diphenhydramine level and sedative and antihistamine effects. Clinical Pharmacology and Therapeutics 23: 375–382, 1978
Colburn WA, Jack ML. Relationships between CSF drug concentrations, receptor binding characteristics, and pharmacokinetic and pharmacokinetic properties of selected 1,4-substituted benzodiazepines. Clinical Pharmacokinetics 13: 179–180, 1987
Colthup PV, Palmer JL. The determination in plasma and pharmacokinetics of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S71–S74, 1989
Duggan DE, Yeh KC, Matalia N, Ditzler CA, McMahon FG. Bio-availability of oral dexamethasone. Clinical Pharmacology and Therapeutics 18: 205–209, 1975
Editorial. Scopoderm: transdermal hyoscine for motion sickness. Drug and Therapeutics Bulletin 27: 91, 1989
Fowler A, Taylor W, Bateman DN. Plasma prochlorperazine assay by high-performance liquid chromatography-electrochemistry. Journal of Chromatography, Biomedical Applications 380: 202–205, 1986
Frey BM, Frey FJ. Clinical pharmacokinetics of prednisone and prednisolone. Clinical Pharmacokinetics 19: 126–146, 1990
Froemming JS, Lam FWY, Jann MW, Davis CM. Pharmacokinetics of haloperidol. Clinical Pharmacokinetics 17: 396–423, 1989
Furlanut M, Benetello P, Baraldo M, Zara G, Montanari G, et al. Chlorpromazine disposition in relation to age. Clinical Pharmacokinetics 18: 329–331, 1990
Golding JF, Strong R, Pethybridge RJ. Time course of effects of oral cinnarizine and hyoscine on task performance. Journal of Psychopharmacology 3: 187–197, 1989
Gralla RJ, Itri LM, Pisko SE, Squilante AE, Kelsen DP, et al. Anti-emetic efficacy of high-dose metoclopramide: randomised trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. New England Journal of Medicine 305: 905–909, 1981
Greenblatt DJ, Ehrenberg BL, Gunderman J, Scavone JM, Tai NT, et al. Kinetic and dynamic study of intravenous lorazepam; comparison with intravenous diazepam. Journal of Pharmacology and Experimental Therapeutics 250: 134–140, 1989a
Greenblatt DJ, Ehrenberg BL, Gunderman J, Locniskar A, Scavone JM, et al. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clinical Pharmacology and Therapeutics 45: 356–365, 1989c
Greenblatt DJ, Harmatz JS, Friedman H, Lockniskar A, Shader RI. A large-sample study of diazepam pharmacokinetics. Therapeutic Drug Monitoring 11: 652–657, 1989b
Greenblatt DJ, Miller LG, Shader RI. Neurochemical and pharmacokinetic correlates of the clinical action of benzodiazepine hypnotic drugs. American Journal of Medicine 88 (Suppl. 3A): 18S–24S, 1990
Grunberg SM, Groshen SG, Robinson DC, Stevenson LL, Sanderson PE. Correlation of antiemetic efficacy and plasma levels of ondansetron. European Journal of Cancer 26: 879–882, 1990
Gupta SK, Ellinwood EH, Nikaido AM, Heatherly DG. Simultaneous modeling of the pharmacokinetic properties of benzodiazepines I: lorazepam. Journal of Pharmacokinetics and Biopharmaceutics 18: 89–102, 1990
Hardy F, Warrington PS, MacPherson JS, Hudson SA, Jefferson GJ, et al. A pharmacokinetic study of high-dose metoclopramide suppositories. Journal of Clinical Pharmacy and Therapeutics 15: 21–24, 1990
Herman RJ, Pham JDV, Szakacs CBN. Disposition of lorazepam in human beings: enterohepatic recirculation and first-pass effect. Clinical Pharmacology and Therapeutics 46: 18–25, 1989
Isah AO, Rawlins MD, Bateman DN. The pharmacokinetics and effects of prochlorperazine in elderly female volunteers. Age and Ageing 21: 27–31, 1992
Jackson RT, Todd NW, Turner Jr JS. Ear nose and throat diseases. In Speight TM (Ed.). Drug treatment 3rd ed., pp. 373–381, Churchill Livingstone, Edinburgh, 1987
Kanto J, Klotz U. Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate. Acta Anaesthesiologica Scandinavica 32: 69–78, 1988
Kearns GL, Butler HL, Kane JK, Carchman SH, Wright GJ. Metoclopramide pharmacokinetics and pharmacodynamics in infants with gastroesophageal reflux. Journal of Pediatric Gastroenterology and Nutrition 7: 823–829, 1988
Kong A-N, Ludwig EA, Slaughter RL, DiStefano PM, DeMasi J, et al. Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of methylprednisolone on serum cortisol and blood histamine in human subjects. Clinical Pharmacology and Therapeutics 46: 616–629, 1989
Koski EMJ, Mattila MAK, Knapik D, Toivanen T, Ruusukallio H, et al. Double blind comparison of transdermal hyoscine and placebo for the prevention of postoperative nausea. British Journal of Anaesthesia 64: 16–20, 1990
Lazarus HM, Bryson JC, Lemon E, Pritchard JF, Blumer J. Antiemetic efficacy and pharmacokinetic analyses of the serotonin antagonist ondansetron (GR 38032F) during multiple-day chemotherapy with cisplatin prior to autologous bone marrow transplantation. Journal of the National Cancer Institute 82: 1776–1778, 1990
Lemberger L, Rubin A, Wolen R, DeSante K, Rowe H, et al. Pharmacokinetics, metabolism and drug-abuse potential of nabilone. Cancer Treatment Reviews 9 (Suppl. B): 17–23, 1982
Loo JCK, Midha KK, McGilvray IJ. Pharmacokinetics of chlorpromazine in normal volunteers. Communications in Psychopharmacology 4: 121–129, 1980
Madej TH, Ellis FR, Tring I. A single dose pharmacokinetic study of Gastrobid Continus and Maxolon in the perioperative period. British Journal of Clinical Pharmacology 26: 747–751, 1988
Meuldermans W, Hurkmans R, Swysen E, Hendricks J, Michiels M, et al. On the pharmacokinetics of domperidone in animals and man III: comparative study on the excretion and metabolism of domperidone in rats, dogs and man. European Journal of Drug Metabolism and Pharmacokinetics 6: 49–69, 1981
Midha KK, Hawes EM, Hubbard JW, Korchinski ED, McKay G. Intersubject variation in the pharmacokinetic of chlorpromazine in healthy men. Journal of Clinical Psychopharmacology 9: 4–8, 1989
Mitchelson F. Pharmacological agents affecting emesis. A review (Part I). Drugs 43: 295–315, 1992
Mollmann H, Rohdewald P, Barth J, Verho M, Derendorf H. Pharmacokinetics and dose linearity testing of methylprednisolone phosphate. Biopharmaceutics and Drug Disposition 10: 453–464, 1989
Moore MJ, Hardy RW, Thiessen JJ, Soldin AJ, Erlkichman C. Rapid development of enhanced clearance after high-dose cyclophosphamide. Clinical Pharmacology and Therapeutics 44: 622–628, 1988
Morrison PJ, Bradbrook ID, Rogers HJ. Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas-liquid chromatography. British Journal of Clinical Pharmacology 7: 349–353, 1979
Paton DM, Webster DR. Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clinical Pharmacokinetics 10: 477–497, 1985
Peroutka SJ, Snyder SH. Anti-emetics: neurotransmitter receptor binding predicts therapeutic effects. Lancet 1: 658–659, 1982
Palazzo MGA, Strunin L. Anaesthesia and emesis. II. Prevention and management. Canadian Anaesthetic Society Journal 31: 407–415, 1984
Plosker GL, Goa KL. Granisetron. A review of its pharmacological properties and therapeutic use as an antiemetic. Drugs 42: 805–824, 1991
Relling MA, Mulhern RK, Dodge RK, Johnson D, Pieper JA, et al. Lorazepam pharmacodynamics and pharmacokinetics in children. Journal of Pediatrics 114: 641–646, 1989
Richter O, Era B, Rienhardt D, Becker B. Pharmacokinetics of dexamethasone in children. Pediatrie Pharmacology 3: 329–337, 1983
Rohdewald P, Molmann H, Barth J, Rehder J, Derendorf H. Pharmacokinetics of dexamethasone and its phosphate ester. Biopharmaceutics and Drug Disposition 8: 205–212, 1987
Rubin A, Lemberger L, Warrick P, Crabtree RE, Sullivan H, et al. Physiologic disposition of nabilone, a cannabinol derivative, in man. Clinical Pharmacology and Therapeutics 22: 85–91, 1977
Saab GA, Shamseddine A. Prolonged chlorpromazine infusion as antiemetic in patients on daily cisplatin infusion. American Journal of Clinical Oncology 11: 470–473, 1988
Saynor DA, Dixon CM. The metabolism of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S75–S77, 1989
Scavone JM, Luna BG, Harmatz JS, Von Moltke L, Greenblatt DJ. Diphenhydramine kinetics following intravenous, oral, and sublingual administration. Biopharmaceutics and Drug Disposition 11: 185–189, 1990
Shaw J, Urquhart J. Programmed, systemic drug delivery by the transdermal route. Trends in Pharmacological Sciences 1: 208–211, 1980
Sidle NR. Antiemetics in pregnancy. In Hawkins DF (Ed.). Drugs and pregnancy: human teratogenesis and related problems, Churchill Livingstone, Edinburgh, 1987
Simons FER, Simons KJ. Pharmacokinetic optimisation of histamine H1-antagonist therapy. Clinical Pharmacokinetics 21: 372–393, 1991
Simons FE, Simons KJ, Chung M, Yeh J. The comparative pharmacokinetics of H1-receptor antagonists. Annals of Allergy 59 (Part II): 20–24, 1987
Simons KJ, Watson WTA, Martin TJ. Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults and children. Journal of Clinical Pharmacology 30: 665–671, 1990
Spector R, Choudhury AK, Chiang C-K, Goldberg MJ, Ghonheim MM. Diphenhydramine in Orientals and Caucasians. Clinical Pharmacology and Therapeutics 28: 229–234, 1980
Taylor WB, Bateman DN. Oral bioavailability of high-dose metoclopramide. European Journal of Clinical Pharmacology 31: 41–44, 1986
Taylor WB, Bateman DN. Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers. British Journal of Clinical Pharmacology 23: 137–142, 1987
Taylor WB, Simpson JM, Bateman DN. High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy. European Journal of Clinical Pharmacology 33: 161–165, 1987
Triozzi PL, Laszlo J. Optimum management of nausea and vomiting in cancer chemotherapy. Drugs 34: 136–149, 1987
Uppington J, Dunnett J, Blogg CE. Transdermal hyoscine and postoperative nausea and vomiting. Anaesthesia 41: 16–20, 1986
Vergin H, Krammer R, Nitsche V. Bioavailability and pharmacokinetics of rectally administered metoclopramide. Arzneimittel-Forschung 40: 679–683, 1990
Vozeh S, Schmidlin O, Taeschner W. Pharmacokinetic drug data. In Mammen GJ (Ed.) Clinical Pharmacokinetics drug data handbook, ADIS Press, Auckland, 1990
Ward A, Holmes B. Nabilone: a preliminary review of its pharmacological properties and therapeutic use. Drugs 30: 127–144, 1985
Ward MJ, Buss DC, Ellershaw J, Nash A, Routledge PA. Bioavailability of intranasal metoclopramide. British Journal of Clinical Pharmacology 28: 616–618, 1989
Wright MR, Axelson JE, Rurak DW, McErlane B, McMorland GH, et al. Linearity of metoclopramide kinetics at doses of 5–20mg. British Journal of Clinical Pharmacology 26: 469–473, 1988a
Wright MR, Axelson JE, Rurak DW, McErlane B, McMorland GH, et al. Effect of haemodialysis on metoclopramide kinetics in patients with severe renal failure. British Journal of Clinical Pharmacology 26: 474–477, 1988b
Zaglama NE, Rosenblum SL, Sartiano GP, Brady ME, Gonzalez MF, et al. Single-high-dose intravenous dexamethasone as an antiemetic in cancer chemotherapy. Oncology 43: 27–32, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Campbell, M., Bateman, D.N. Pharmacokinetic Optimisation of Antiemetic Therapy. Clin-Pharmacokinet 23, 147–160 (1992). https://doi.org/10.2165/00003088-199223020-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199223020-00006