Bryson S M, McGovern E M, Kelman A W, White K, Addis G J, Whiting B
Br J Clin Pharmacol. 1985 Jun;19(6):757-66. doi: 10.1111/j.1365-2125.1985.tb02711.x.
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)].
对19例接受静脉注射环磷酰胺单药化疗的支气管癌患者给予大剂量胃复安输注（10mg/kg）。观察到胃复安处置存在相当大的个体间差异。平均清除率为0.33±0.13（标准差）l h⁻¹ kg⁻¹，稳态分布容积平均为3.8±1.2（标准差）l/kg，平均消除半衰期为8.3±4.4（标准差）h。这些结果与先前报道的给予常规剂量的年轻健康志愿者的平均值（分别为0.70 l h⁻¹ kg⁻¹、2.2 l/kg和2.6 h）显著不同。发现血清尿素、血清肌酐与胃复安清除率之间存在显著相关性。胃复安治疗方案耐受性良好，除两名患者外，在预防恶心和呕吐方面完全有效。为达到并维持目标血清胃复安浓度1μg/ml，我们现在先在30分钟内给予3.61mg/kg的负荷输注，然后以0.36mg kg⁻¹ h⁻¹的维持输注持续10小时。环磷酰胺通常在第二次输注时同时给药。对于有轻度肾功能损害证据的患者，盐酸胃复安的维持输注速率应根据预测的个体清除率值进行调整；CL（l h⁻¹ kg⁻¹）=0.57 - [0.036×尿素（mmol/l）]。
