Quantitative determination of domperidone in rat plasma by high-performance liquid chromatography with fluorescence detection.

Determination of metoclopramide and two of its metabolites using a sensitive and selective gas chromatographic-mass spectrometric assay.

Liquid chromatographic analysis of alizapride and metoclopramide in human plasma and urine using solid-phase extraction.

The current knowledge on treatment of emesis induced by cytostatic therapy is reviewed. A description of the multiple causative mechanisms shows the rationality of combining antiemetic agents in the prophylaxis of nausea and vomiting, especially when induced by highly emetogenic chemotherapeutic agents as cisplatin. The need for prevention instead of treatment is demonstrated by explaining the syndrome of anticipatory nausea and vomiting. Promising efficacy and lack of serious side effects are reported for newly developed 5-hydroxytryptamine3 antagonists.

Nausea and Vomiting Induced by Cytostatic Agents

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.

/pdf/linearity-of-metoclopramide-kinetics-at-doses-of-5-20-mg-14ayb1g37a.pdf

Linearity of metoclopramide kinetics at doses of 5-20 mg

Eleven male subjects aged 24 to 58 yr received cisplatin, 90 to 120 mg/m2 iv, in combination with other cytostatic drugs such as doxorubicin HC1 and bleomycin. To prevent emesis, two high-dose metoclopramide regimens were started 2 hr before cytostatic therapy. Regimen A (n = 7) consisted of a loading dose infusion of 1 mg/kg/hr over 2 hr, followed by a maintenance infusion of 0.5 mg/kg/hr over 24 hr (total dose was 14 mg/kg in each cytostatic cycle). Regimen B (n = 6) consisted of half the metoclopramide dose. The following kinetics were derived from the metoclopramide steady-state plasma levels and the t½ of the elimination phase 26 to 38 hr after dosing (median value and range are listed): Steady-state plasma concentration in group A and group B was 750 (480 to 1520) and 360 (300 to 480) ng/ml plasma. Drug clearance in group A and group B was 0.67 (0.3 to 1.0) and 0.70 (0.5 to 0.8) l/hr/kg. Volumes of drug distribution in group A and group B were 4.4 (1.9 to 6.5) and 4.3 (3.2 to 5.9) l/kg. Values for the t½ in the elimination phase in group A and group B were 4.7 (3.0 to 5.4) and 4.3 (3.7 to 5.1) hr. It appears that metoclopramide kinetics at high doses were dose linear, i.e., without evidence of cumulation. There were few side effects; vomiting was effectively suppressed by both regimens.



Clinical Pharmacology and Therapeutics (1985) 37, 43–47; doi:10.1038/clpt.1985.9

Metoclopramide kinetics at high‐dose infusion rates for prevention of cisplatin‐induced emesis

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Metoclopramide kinetics at high‐dose infusion rates for prevention of cisplatin‐induced emesis