Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

6. Project II: Pharmacokinetic of transmucosal nasal delivered midazolam – impact of adjuvants
midazolam serum concentration [ug/l]
90.0
80.0
70.0
60.0
50.0
40.0
30.0
20.0
10.0
1mg, i.v.
1mg, P1
1mg, P2
1mg, P3
3mg, P4
3mg, P5
0.0
0 10 20 30 40 50 60
Time [min]
Figure 6-7: Midazolam serum concentration (mean) following i.v. and nasal administration of 1 mg
midazolam (Preparation 1, 2, and 3) and nasal administration of 3 mg midazolam (Preparation 4 and 5)
to 8 volunteers. This figure displays midazolam concentrations asessed predose, 1, 2.5, 5, 10, 15, 20,
30, 45, and 60 minutes after midazolam administration.
Table 6-3 summarizes the assessed pharmacokinetic parameters following i.v. and nasal
midazolam delivery. Time to reach maximal midazolam serum concentration (t max ) after nasal
administration of Preparation 1 to 5 ranged from 7.1 ± 0.6 min (Preparation 5) to 11.7 ± 2.4 min
(Preparation 4). Mean systemic bioavailability (F) of midazolam after nasal administration of test
preparation varies from 93% (Preparation 2) to 78% (Preparation 5).
Differences of systemic midazolam bioavailability following nasal midazolam administration were
not significant. Clearance (Cl) and half life (t 1/2 ) were constant and independent of midazolam
administration modality.
Katja Suter-Zimmermann Page 69 of 188 University of Basel, 2008