Greenblatt D J, Abernethy D R, Locniskar A, Harmatz J S, Limjuco R A, Shader R I
Anesthesiology. 1984 Jul;61(1):27-35.
The effects of age, sex, and obesity on the kinetics of single intravenous (iv) and oral doses of midazolam were evaluated in healthy volunteers who received 2.5-5 mg of iv midazolam on one occasion and 5-10 mg orally on another. Kinetics were determined from multiple plasma midazolam concentrations measured during 24 h after dosage. Midazolam elimination half-life (t1/2) after iv dosage was significantly prolonged in elderly (aged 60-74 yr) versus young (24-33 yr) males (5.6 vs. 2.1 hours, P less than 0.01) and total clearance was significantly reduced (4.4 vs. 7.8 ml X min-1 X kg-1, P less than 0.01), leading to increased systemic availability of the oral dose (50% vs. 41%, P less than 0.05). However total volume of distribution calculated by the area method (Vd) (1.6 vs. 1.3 1/kg) and protein binding (3.5 vs. 3.4% unbound) did not differ between groups. Among women there were no significant differences between elderly (64-79 yr) and young (23-37 yr) volunteers in t1/2 (4.0 vs. 2.6 h), clearance (7.5 vs. 9.4 ml X min-1 X kg-1), Vd (2.1 vs. 2.0 1/kg), protein binding (3.7% vs. 3.7% unbound), or oral bioavailability (38% vs. 36%). In obese volunteers (mean weight 117 kg; 173% of ideal weight) versus control subjects of normal weight (66 kg, 95% of ideal weight) matched for age, sex, and smoking habits, midazolam Vd was increased significantly (311 vs. 114 1, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
在健康志愿者中评估了年龄、性别和肥胖对单次静脉注射（iv）和口服咪达唑仑动力学的影响。这些志愿者一次接受2.5 - 5mg静脉注射咪达唑仑，另一次接受5 - 10mg口服咪达唑仑。通过给药后24小时内多次测量血浆咪达唑仑浓度来确定动力学。与年轻男性（24 - 33岁）相比，老年男性（60 - 74岁）静脉注射咪达唑仑后的消除半衰期（t1/2）显著延长（5.6对2.1小时，P小于0.01），总清除率显著降低（4.4对7.8ml·min⁻¹·kg⁻¹，P小于0.01），导致口服剂量的全身可用性增加（50%对41%，P小于0.05）。然而，通过面积法计算的分布总体积（Vd）（1.6对1.3l/kg）和蛋白结合率（未结合率3.5%对3.4%）在两组之间没有差异。在女性中，老年志愿者（64 - 79岁）和年轻志愿者（23 - 37岁）在t1/2（4.0对2.6小时）、清除率（7.5对9.4ml·min⁻¹·kg⁻¹）、Vd（2.1对2.0l/kg）、蛋白结合率（未结合率3.7%对3.7%）或口服生物利用度（38%对36%）方面没有显著差异。在年龄、性别和吸烟习惯相匹配的肥胖志愿者（平均体重117kg；理想体重的173%）与正常体重的对照受试者（66kg，理想体重的95%）中，咪达唑仑的Vd显著增加（311对114l，P小于0.001）。（摘要截于250字）
