Optimizing Metoclopramide Control of Cisplatin-Induced Emesis

Meyer, B. Robert

doi:10.7326/0003-4819-100-3-393

Cited by 76 publications

(30 citation statements)

References 4 publications

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“…First, our subjects were younger with a median age of 41 years compared to 55 years in the trial of Kris and coworkers. Thus age may be an important factor as it has been shown that elderly patients are more sensitive to the antiemetic effects of metoclopramide (Meyer et al, 1984). Secondly, the differences in the two trial populations, study designs, chemotherapeutic regimens and criteria for evaluating response also provide additional explanations for the disparate re.sults.…”

Section: Resultsmentioning

confidence: 99%

Antiemetic efficacy of high-dose dexamethasone: Randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine

Al‐Idrissi

Ibrahim²,

Abdullah³

et al. 1988

Br J Cancer

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Silmmary A double-blind, randomized, crossover study was conducted to compare the efficacy and safety of high-dose dexamethasone (Protocol D) with a combination of dexamethasone, metoclopramide and diphenhydramine (Protocol DMD) in the management of chemotherapy-induced nausea and vomiting in cancer patients. All entered patients had received no prior chemotherapy. During the study chemotherapy was administered on an inpatient basis. The majority of patients (94%) were treated with cytotoxic drugs of significant emetogenic activity and 40% of the study group received cis-platin-containing combinations.Of DMD and 9 (15%) found no difference between the two regimens.We conclude that, while the short DMD protocol has an antiemetic activity equivalent in its effectiveness to D, its associated adverse reactions would minimize its usefulness. Therefore, further investigations should be conducted to find a safer and more potent combination of antiemetics suitable for therapy in an outpatient setting.Nausea and vomiting are the most common and potentially grave complications of anticancer therapy (Laszlo & Lucas, 1981;Morran et al., 1979;Seigel & Long, 1981). Moreover, emesis is an important limiting factor in the administration of cytotoxic therapy (Seigel & Long, 1981). Total prevention of chemotherapy-induced nausea and vomiting is paramount in improving patients' acceptance of cytotoxic drugs.Various groups of antiemetics with varying degree of efficacy and modes of action have been tested (Laszlo, 1983;Moertel & Reitemeier, 1969;Moertel et al., 1963;Wampler, 1983). Dexamethasone has been shown to exhibit significant antiemetic activity in the past few years (Aapro & Plezia, 1983;Cassileth et al., 1983Cassileth et al., ,1984Markman et al., 1984). Recently also, in a randomized, double-blind, crossover study, we demonstrated conclusively that high-dose dexamethasone is more effective as an antiemetic and safer than high-dose metoclopramide in patients who are mainly receiving non-cis-platin emetogenic chemotherapy (Ibrahim et al., 1986). However, the dosages and schedule of the antiemetics used in that trial were not suitable for outpatient management.The administration of combinations of antiemetic drugs which would act at different receptor sites should improve their antiemetic potential through complete neuroreceptor blockade (Bruera et al., 1983;Krebs et al., 1985;Mason et al., 1982;Morran et al., 1979). Furthermore, combining two or more antiemetics should minimise the adverse effects produced by the constituent agents given singly in higher doses. The efficacy and safety of a short course of the combination of dexamethasone, metoclopramide and diphenhydramine (Protocol DMD) have been demonstrated recently (Kris et al., 1985). However, the DMD regimen has never been tested in a double-blind and randomized trial against the well established antiemetic protocols.We now present the outcome of a randomized, doubleblind, crossover study comparing the effectiveness of highdose dexamethasone (Protocol D) with a short...

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Section: Resultsmentioning

confidence: 99%

Antiemetic efficacy of high-dose dexamethasone: Randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine

Al‐Idrissi

Ibrahim²,

Abdullah³

et al. 1988

Br J Cancer

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“…First, there is a metoclopramide dose concentration relationship to the metoclopramide serum levels regardless of the species or route of administration, and second, the rat, rabbit and dog eliminate metoclopramide from serum much faster than humans do (Bakke & Segura 1976;Bateman et al 1980Bateman et al , & 1983Brechot et al 1991;Citron et al 1987;Graffner et al 1979;Meyer et al 1984;Tam et al 1981;Tyson et al 1989).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, Toxicity, Side Effects, Receptor Affinities and in vitro Radiosensitizing Effects of the Novel Metoclopramide Formulations, Sensamide and Neu‐Sensamide

Pero¹,

Olsson²,

Simanaitis

et al. 1997

Pharmacology & Toxicology

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Abstract:Metoclopramide is a drug which has experienced worldwide use in the clinic for over 30 years as an antiemetic. Recently, it has also been shown to possess radio-and chemosensitizing properties in both animal tumour models and humans at the higher dose of 2 mg/kg. Two new metoclopramide formulations are being clinically developed and they differ mainly in whether the pH of their formulations are acidic (pH 2.5-3.5) or neutral (pH 6.5-7.0). Here we report that intramuscular administration of neutral metoclopramide is about 100% bioavailable, safer and with reduced side effects compared to acidic metoclopramide delivered by intramuscular injection to rats within the dose range of 3.5 to 14 mgikg. The intramuscular administration of metoclopramide was also about 100% bioavailable compared to the intravenous route of administration. Furthermore, neutral metoclopramide had significantly decreased affinity for dopamine D2 receptors and increased affinity for 5-hydr~xytryptamine~ receptors, but the radiosensitizing potency was the same, when compared to equimolar concentrations of acidic metoclopramide. Taken together these data support the continued development of neutral metoclopramide for high dose intramuscular administration of metoclopramide for future clinical use as both an antiemetic and radiosensitizer.

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“…The log of the plasma drug concentration was stable from 2-9 h after administration suggesting that this preparation would be suitable for 8 or 12 hourly administration. However the delay in Cmax may result in delayed or complete absence of clinical effect since a rapid rise in CNS concentration may be important for therapeutic effect (Bateman et al, 1978(Bateman et al, , 1979 McGovern et al, 1983;Taylor & Bateman, 1983;Meyer et al, 1984). Much lower plasma drug concentrations 20 ng ml-' increase gastric emptying after intravenous administration (Bateman et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

A single dose pharmacokinetic study of Gastrobid Continus and Maxolon in the perioperative period.

Madej

Ellis

Tring

1988

Brit J Clinical Pharma

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1 A single dose pharmacokinetic comparison of Gastrobid Continus and Maxolon was carried out perioperatively in two groups of 12 gynaecological patients; each group comprised six patients for major surgery and six patients for minor surgery. 2 The areas under the plasma drug concentration-time curves were similar after both preparations. 3 In the minor surgery group after Gastrobid Continus the plasma drug concentrationtime curve was wider at half Cmax (P < 0.01), Cmax was reduced (P < 0.05) and delayed (median (range) 4 (3-6) vs 2.5 (2-4) h) compared with Maxolon, and the log of the metoclopramide concentration did not have a linear relationship with time from 2-9 h. 4 A flattening of the plasma drug concentration-time curve was the only difference between the two preparations in the major surgery groups. 5 The plasma drug concentration-time curve was wider (P < 0.05) at half Cmax in the minor compared with the major surgery groups receiving Gastrobid Continus. 6 Pharmacokinetic parameters were similar for Maxolon in both surgical groups. 7 Sustained release pharmacokinetic characteristics were most pronounced in the minor surgery group which did not receive opiate medication but in which there were more moderately anxious patients prior to induction and in whom anxiety may have delayed gastric emptying.

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Optimizing Metoclopramide Control of Cisplatin-Induced Emesis

Cited by 76 publications

References 4 publications

Antiemetic efficacy of high-dose dexamethasone: Randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine

Antiemetic efficacy of high-dose dexamethasone: Randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine

Pharmacokinetics, Toxicity, Side Effects, Receptor Affinities and in vitro Radiosensitizing Effects of the Novel Metoclopramide Formulations, Sensamide and Neu‐Sensamide

A single dose pharmacokinetic study of Gastrobid Continus and Maxolon in the perioperative period.

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