Midazolam pharmacokinetics following intravenous and buccal administration

Abstract

Aims: Midazolam has good anxiolytic qualities and is a well established premedication agent before anaesthesia or short surgical procedures. The objective of the present study was to determine pharmacokinetic data from individual plasma concentration profiles obtained following intravenous and buccal administration of midazolam.

Methods: Eight young healthy volunteers received single doses of 5 mg midazolam i.v. and after a period of 1 week buccally in a cross over manner. Blood samples were obtained up to 480 min. The measurement of plasma midazolam concentrations was by gas-chromatography.

Results: The maximum plasma concentration was 55.9 ng ml(-1) (range 35.6-77.9 ng ml(-1)) at 30 min (range 15-90 min) following buccal administration. AUC was calculated to be 15016 ng ml(-1) min (s.d. 3778 ng ml(-1) min) following i.v. and 11191 ng ml(-1) min (s.d. 1777 ng ml(-1) min) following buccal midazolam. This gave a mean midazolam bioavailability of 74.5%.

Conclusions: The pharmacokinetic data presented in this study demonstrate a high bioavailability and reliable plasma concentrations following buccal midazolam. The clinical benefit of buccal midazolam may be in particular patient controlled premedication or sedation in adults.

Figure 1

Volunteer sedation following intravenous (•) and buccal (▴) administration of 5 mg midazolam (1 ml=5 mg). Depicted are the number of volunteers who assessed themselves sedated.

Figure 2

Plasma concentration curves following intravenous (—•—) and buccal (—▴—) administration of 5 mg midazolam (mean±s.d.).