Björkman S, Rigemar G, Idvall J
Malmö University Hospital, Sweden.
Br J Anaesth. 1997 Nov;79(5):575-80. doi: 10.1093/bja/79.5.575.
The aim of this study was to determine the bioavailability and absorption kinetics of midazolam given as an intranasal (i.n.) spray. In addition, plasma concentrations of the active metabolite, 1-hydroxymidazolam, were measured to give an indication of enteral absorption. An i.v. and i.n. midazolam dose were given in a crossover study to 14 adult surgical patients. Individual uptake profiles of i.n. midazolam were estimated by numerical deconvolution. After an i.n. dose of 0.15 mg kg-1, maximum arterial plasma concentrations were 192 (SD 48) micrograms litre-1 at 14 (2) min. Uptake of midazolam was rapid and bioavailability was 83 (15)%. Formation of the 1-hydroxy metabolite after i.n. administration did not exceed that after the i.v. dose. This demonstrates that under optimal conditions absorption of midazolam via the nasal mucosa was virtually complete. In this case little midazolam was swallowed and subjected to first-pass metabolism in the liver and therefore pharmacologically important amounts of active metabolite were not produced. Routinely administering i.n. midazolam under the assumption that the bioavailability is approximately 50% (as reported previously in the literature) may lead to overdosing in some patients.
本研究的目的是测定以鼻内（i.n.）喷雾剂形式给予咪达唑仑的生物利用度和吸收动力学。此外，还测量了活性代谢物1-羟基咪达唑仑的血浆浓度，以指示肠道吸收情况。在一项交叉研究中，对14名成年外科手术患者给予静脉注射（i.v.）和鼻内咪达唑仑剂量。通过数值反卷积估计鼻内咪达唑仑的个体摄取曲线。给予0.15 mg kg-1的鼻内剂量后，在14（2）分钟时最大动脉血浆浓度为192（标准差48）μg/L。咪达唑仑的摄取迅速，生物利用度为83（15）%。鼻内给药后1-羟基代谢物的形成不超过静脉注射剂量后的形成。这表明在最佳条件下，通过鼻黏膜吸收的咪达唑仑几乎是完全的。在这种情况下，很少有咪达唑仑被吞咽并在肝脏中进行首过代谢，因此没有产生药理学上重要量的活性代谢物。在生物利用度约为50%（如先前文献报道）的假设下常规给予鼻内咪达唑仑可能会导致一些患者用药过量。
