The pharmacokinetics of metoclopramide in man with observations in the dog.

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

“…and oral doses from 5-20 mg (Graffner et al, 1979;Bateman et al, 1980;Bateman, 1983). This finding has been widely reported and is included in common clinical references consulted by both physicians and pharmacists (USPDI, 1984).…”

“…It appeared that there may have been several experimental reasons for the possibly erroneous conclusions drawn in the literature, pertaining to the claimed dose-dependent elimination and the precise extent of bioavailability of metoclopramide. More specifically, in many earlier studies the relatively insensitive assay procedures used allowed metoclopramide to be measured in plasma for only a relatively short period of time (6-8 h) (Bateman et al, 1980;Graffner et al, 1979). Truncation of the sampling interval in pharmacokinetic studies has long been known to produce underestimates of the elimination half-life (Gibaldi & Weintraub, 1971).…”

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

“…Furthermore, in patients with impaired renal function there is an increased risk of accumulation as at routine clinical doses the half-life of metoclopramide is considerably prolonged (Bateman et al, 1981). As a large proportion of metoclopramide is metabolized, probably in the liver (Bateman et al, 1980), elimination is also likely to be impaired in patients with abnormal liver function, for example patients with secondary deposits in the liver. This study has shown that the kinetics of metoclopramide, when given in large doses, are linear, despite the dose-dependent kinetics previously reported at conventional doses (Bateman et al, 1980;Graffner et al, 1979 (Gralla et al, 1981a).…”

“…As a large proportion of metoclopramide is metabolized, probably in the liver (Bateman et al, 1980), elimination is also likely to be impaired in patients with abnormal liver function, for example patients with secondary deposits in the liver. This study has shown that the kinetics of metoclopramide, when given in large doses, are linear, despite the dose-dependent kinetics previously reported at conventional doses (Bateman et al, 1980;Graffner et al, 1979 (Gralla et al, 1981a). We calculate from our results that a patient given a loading dose of 3.1 mg/kg metoclopramide followed by an infusion of 0.4 mg kg-h-1 should achieve a steady-state plasma concentration of 1 ,ug/ml.…”

“…infusion, calculated from known pharmacokinetic parameters (Clark & Smith, 1981). Previous studies suggest, however, that metoclopramide has dose-dependent kinetics (Bateman et al, 1980;Graffner et al, 1979) Six patients completed the study receiving each of the three dosage schedules of metoclopramide. One patient died after two courses of chemotherapy, one patient withdrew from the study after two courses because she disliked staying in hospital overnight, and a third patient Table 1).…”