Relative bioavailability of midazolam following sublingual versus oral administration in healthy volunteers.

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Abstract
The extent of bioavailability of midazolam following sublingual and oral administration were evaluated. Three healthy volunteers received a single 15-mg dose of midazolam maleate by sublingual and oral routes on two occasions in a crossover design. Concentrations of midazolam in plasma during 4 h after each dose were measured by gas-liquid chromatography with an electron-capture detector. The mean UC0-4 value following sublingual administration was significantly greater than that following oral administration (14889 vs 3594 ng .cntdot. min/ml, p < 0.05). The peak plasma concentration after sublingual dose was also significantly higher than that after oral administration (p < 0.05). The mean AUC0-4 value of midazolam after sublingual administration was increased four times compared with that after oral administration, possibly due to avoidance of first-pass effect. Thus, the clinical effects of midazolam may likewise be enhanced by sublingual administration of midazolam.

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