Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

6. Project II: Pharmacokinetic of transmucosal nasal delivered midazolam – impact of adjuvants
Delta RT and delta ISI refer to the difference of the assessed RT and ISI at 20 min, 120 min, and
240 min after midazolam administration and the corresponding parameter assessed previous to
midazolam administration. In Figure 6-12 and Figure 6-13 delta RT and delta ISI assessed after
administration of study medication are displayed.
300
250
Delta Interstimulus Interval [ms]
200
150
100
50
0
-50
1mg, i.v. 1mg, nasal P1 1mg, nasal P2 1mg, nasal P3 3mg, nasal P4 3mg, nasal P5
20min 14.5 9.3 27.3 15.8 121.0 150.1
120min 29.6 5.4 23.6 21.4 34.0 77.0
240min 21.3 -7.1 -1.9 10.0 26.6 12.4
Figure 6-12: Delta interstimulus interval (ISI) assessed by CRTT. Delta interstimulus interval refers to
the difference between the ISI at 20 min, 120 min, and 240 min after midazolam application and the
corresponding ISI.
300
250
Delta Reaction Time [ms]
200
150
100
50
0
-50
1mg, i.v. 1mg, nasal P1 1mg, nasal P2 1mg, nasal P3 3mg, nasal P4 3mg, nasal P5
20min 5.6 3.4 9.6 13.6 70.4 87.5
120min 13.8 0.6 5.0 13.5 20.4 46.8
240min 3.1 -8.4 -15.6 -5.0 7.5 9.8
Figure 6-13: Delta reaction time (RT) assessed by CRTT. Delta RT refers to the difference between the
RT assessed 20 min, 120 min, and 240 min after midazolam application and the corresponding RT
assessed predose.
Katja Suter-Zimmermann Page 76 of 188 University of Basel, 2008