DOSE DEPENDENT PHARMACOKINETICS OF MIDAZOLAM
DOSE DEPENDENT PHARMACOKINETICS OF MIDAZOLAM
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DOI：
10.1007/bf00547375
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发表时间：
1985-01-01
影响因子：
2.9
通讯作者：
PATEL, IH
中科院分区：
文献类型：
--
作者：
BORNEMANN, LD;MIN, BH;PATEL, IH
12名健康受试者分别口服7.5、15和30 mg咪达唑仑溶液，研究咪达唑仑和1-羟甲基咪达唑仑的药代动力学。与7.5 mg剂量相比，咪达唑仑和1-羟甲基咪达唑仑的Cmax和AUC参数在15 mg剂量后成比例增加，在30 mg剂量后成比例增加。咪达唑仑的t1/2在7.5至15 mg剂量之间保持相对不变，但在30 mg剂量后略有增加，但显着增加。这些数据表明咪达唑仑和1-羟甲基咪达唑仑在7.5-15 mg口服剂量范围内呈线性关系。然而，在30毫克剂量后，咪达唑仑的全身利用度和1-羟甲基咪达唑仑的AUC似乎大于较低剂量的预期，可能是由于咪达唑仑的首过代谢饱和所致。在治疗使用的条件下，这预计不会有任何临床意义。
The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This is not expected to have any clinical significance under the conditions of therapeutic use.