Pharmacokinetics and efficacy of high‐dose metoclopramide given by continuous infusion for the control of cytotoxic drug‐induced vomiting.

Taylor, W.; Proctor, SJ; Bateman, D. N.

doi:10.1111/j.1365-2125.1984.tb02529.x

Cited by 23 publications

(19 citation statements)

References 9 publications

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“…Our observation, in man, that metoclopramide does not undergo dose-dependent kinetics also contrasts with our findings in the rat (Tam et al, 1981;Kapil et al, 1984) where metoclopramide was noted to undergo non-linear kinetics. However, studies in cancer chemotherapy at doses greater than 0.5 mg kg-' (Taylor et al, 1984;Bryson et al, 1985) and 20-100 mg are consistent with linear kinetics.…”

Section: Discussionmentioning

confidence: 91%

Linearity of metoclopramide kinetics at doses of 5‐20 mg.

Wright

Axelson

Rurak

et al. 1988

Brit J Clinical Pharma

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The disposition of metoclopramide was studied on a four-way crossover basis in six healthy non-smoking volunteers. The linearity of kinetic parameters and absolute bioavailability of metoclopramide were examined. In contrast to previous reports, metoclopramide obeyed linear kinetics over oral doses ranging from 5 to 20 mg. The absolute bioavailability of metoclopramide was 0.76 ± 0.38 (mean ± s.d.) from the oral dosage forms examined in this study.

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Section: Discussionmentioning

confidence: 91%

Linearity of metoclopramide kinetics at doses of 5‐20 mg.

Wright

Axelson

Rurak

et al. 1988

Brit J Clinical Pharma

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“…This infusion regimen is proposed as a recommendation for the 'average' patient with normal renal and hepatic function. A similar loading and maintenance infusion approach has been proposed recently by Taylor et al (1984). The infusion protocol is simple and the resultant serum levels relatively stable.…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease.

Bryson¹,

McGovern²,

Kelman³

et al. 1985

Brit J Clinical Pharma

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High dose metoclopramide infusions (10 mg/kg) were administered to nineteen patients with bronchial carcinoma who were receiving intravenous cyclophosphamide as single agent chemotherapy. Considerable interindividual variability in metoclopramide disposition was observed. Mean clearance was 0.33 +/‐ 0.13 (s.d.) l h‐1 kg‐1, mean volume of distribution at steady state was 3.8 +/‐ 1.2 (s.d.) l/kg and mean elimination half‐life was 8.3 +/‐ 4.4 (s.d.) h. These results were significantly different from mean values previously reported for young healthy volunteers given conventional doses (0.70 l h‐1 kg‐1, 2.2 l/kg and 2.6 h respectively). Significant correlations were found between serum urea, serum creatinine and metoclopramide clearance. The metoclopramide regimens were well tolerated and, with the exception of two patients, were completely effective in the prevention of nausea and vomiting. To achieve and maintain target serum metoclopramide concentrations of 1 microgram/ml, we now administer a loading infusion of 3.61 mg/kg over 30 min followed by a maintenance infusion of 0.36 mg kg‐1 h‐1 for 10 h. Cyclophosphamide is normally administered concurrently with the second infusion. For patients with evidence of mild renal impairment, the maintenance infusion rate of metoclopramide hydrochloride should be adjusted according to the predicted individual clearance value; CL (l h‐1 kg‐1) = 0.57 ‐ [0.036 X urea (mmol/l)].

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“…Clearance values reported after high-dose metoclopramide are in the range 0.3 to 0.4 L/kg/h (Bryson et al 1985;Taylor et al 1984;Taylor & Bateman 1985), with the exception of Saller et al (l985a) who obtained values around 0.7 L/kg/h. The difference may lie in the heterogeneity of the study populations, since the patients in Saller's group were younger (24 to 58 years) with creatinine clearance values of greater than 60 mlfmin and normal liver function.…”

Section: Eliminationmentioning

confidence: 90%

“…The alternative approach to high-dose parenteral therapy is to utilise a constant infusion technique which maintains stable serum concentrations and simplifies the administration procedure (Bryson et al 1985;Saller et al 1985;Taylor et al 1984). The requirement for a loading dose is important from a pharmacokinetic viewpoint because steady-state will not be achieved until 4 or 5 halflives have elapsed.…”

Section: Eliminationmentioning

confidence: 98%

Pharmacokinetics of High-Dose Metoclopramide in Cancer Patients

McGovern

Grevel

Bryson

1986

Clinical Pharmacokinetics

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The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.

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Pharmacokinetics and efficacy of high‐dose metoclopramide given by continuous infusion for the control of cytotoxic drug‐induced vomiting.

Cited by 23 publications

References 9 publications

Linearity of metoclopramide kinetics at doses of 5‐20 mg.

Linearity of metoclopramide kinetics at doses of 5‐20 mg.

The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease.

Pharmacokinetics of High-Dose Metoclopramide in Cancer Patients

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