Bornemann L D, Min B H, Crews T, Rees M M, Blumenthal H P, Colburn W A, Patel I H
Eur J Clin Pharmacol. 1985;29(1):91-5. doi: 10.1007/BF00547375.
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.
在12名健康受试者口服7.5毫克、15毫克和30毫克溶液剂量的咪达唑仑后，对咪达唑仑和1-羟甲基咪达唑仑的药代动力学进行了研究。与7.5毫克剂量相比，15毫克剂量后咪达唑仑和1-羟甲基咪达唑仑的Cmax和AUC参数成比例增加，30毫克剂量后增加幅度超过比例。7.5毫克和15毫克剂量之间咪达唑仑的t1/2保持相对恒定，而30毫克剂量后略有但显著增加。这些数据表明，7.5毫克至15毫克口服剂量范围内咪达唑仑和1-羟甲基咪达唑仑的药代动力学呈线性。然而，30毫克剂量后，咪达唑仑的全身可用性和1-羟甲基咪达唑仑的AUC似乎高于较低剂量预期的值，这可能是由于咪达唑仑首过代谢饱和所致。在治疗使用条件下，预计这不会有任何临床意义。
