Saller R, Hellenbrecht D, Briemann L, Hellstern A, Hess H, Mitrou P, Hodgson M, Achtert G, Brockmann P, Hausleiter H J
Clin Pharmacol Ther. 1985 Jan;37(1):43-7. doi: 10.1038/clpt.1985.9.
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 HCl 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 t1/2 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 t1/2 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.
11名年龄在24至58岁之间的男性受试者接受了静脉注射顺铂，剂量为90至120mg/m²，并与其他细胞毒性药物如盐酸阿霉素和博来霉素联合使用。为预防呕吐，在细胞毒性治疗前2小时开始采用两种高剂量甲氧氯普胺方案。方案A（n = 7）包括在2小时内以1mg/kg/小时的负荷剂量输注，随后在24小时内以0.5mg/kg/小时的维持剂量输注（每个细胞毒性周期的总剂量为14mg/kg）。方案B（n = 6）的甲氧氯普胺剂量为方案A的一半。以下动力学数据来自甲氧氯普胺稳态血浆水平以及给药后26至38小时消除相的t1/2（列出中位数和范围）：A组和B组的稳态血浆浓度分别为750（480至1520）和360（300至480）ng/ml血浆。A组和B组的药物清除率分别为0.67（0.3至1.0）和0.70（0.5至0.8）l/小时/千克。A组和B组的药物分布容积分别为4.4（1.9至6.5）和4.3（3.2至5.9）l/千克。A组和B组消除相的t1/2值分别为4.7（3.0至5.4）和4.3（3.7至5.1）小时。似乎高剂量甲氧氯普胺的动力学呈剂量线性，即无蓄积迹象。副作用很少；两种方案均有效抑制了呕吐。
