Bakke O M, Segura J
J Pharm Pharmacol. 1976 Jan;28(1):32-9. doi: 10.1111/j.2042-7158.1976.tb04019.x.
The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration.
已在大鼠、兔和犬中对甲氧氯普胺的吸收和消除进行了研究。采用薄层色谱法并结合光密度测定法分析未变化的药物及其代谢产物。N-去乙基化是一种重要的I相代谢反应，与葡萄糖醛酸和硫酸盐结合是主要的代谢途径，尤其是在兔中。静脉给药后的药代动力学参数显示种间差异很小。观察到符合一级消除动力学，半衰期短，表观分布容积高（大于1.1 kg(-1)）。口服高剂量药物后可见明显的种间差异。给大鼠口服后，甲氧氯普胺消除缓慢。兔和犬的研究结果表明，肝脏在口服给药后降低未变化的甲氧氯普胺的全身可用性方面发挥着积极作用。
