Absolute Bioavailability of Microdosed Midazolam After Buccal Administration Is Dependent on Buccal Exposure Time

作者: Jana Grass , Peter Rose , Jürgen Burhenne , Antje Blank , Walter Emil Haefeli

DOI: 10.1002/JCPH.1751

关键词:

摘要: Midazolam is an established probe drug to assess cytochrome P450 3A activity (phenotyping). Microdosed midazolam increasingly used for this purpose; a buccal formulation might be of advantage, but absorption occur. We therefore tested in single-center, open-label clinical trial with 12 healthy volunteers the absolute bioavailability 10 μg after administration relation exposure time. In drinking solution, there was increase (area under plasma concentration-time curve from time 0 infinity) increasing apparent saturation at 100-second exposure. Absolute increased 27.8% (95% confidence interval, 23.5-32.9) solution (0 seconds) 66.1% 60.0-72.8) no further 150 seconds. A Hill equation described dependency maximal as 64.5% and resulting half 16 conclusion, highly dependent on time, even few seconds will due absorption. This needs taken into account any midazolam.

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