Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

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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
6. Project II: Pharmacokinetic of transmucosal nasal delivered midazolam – impact of adjuvants Figure 6-14 shows the correlation of midazolam serum concentration time profile and performance of CRTT (delta RT and delta ISI). 180 1mg midazolam, nasal P1 100 180 1mg midazolam, i.v. 100 160 90 160 90 140 80 140 80 120 100 80 60 70 60 50 40 30 120 100 80 60 70 60 50 40 30 40 20 40 20 20 10 20 10 0 0 2 3 5 10 15 20 30 45 60 120 180 240 360 0 0 0 2 3 5 10 15 20 30 45 60 120 180 240 360 0 Time [ms] 180 160 140 120 100 80 60 40 20 0 1mg midazolam, nasal P2 0 2 3 5 10 15 20 30 45 60 120 180 240 360 100 90 80 70 60 50 40 30 20 10 0 180 160 140 120 100 80 60 40 20 0 3mg midazolam, nasal P4 0 2 3 5 10 15 20 30 45 60 120 180 240 360 100 90 80 70 60 50 40 30 20 10 0 Midazolam serum concentration [µg/l] 180 1mg midazolam, nasal P3 100 180 3mg midazolam, nasal P5 100 160 90 160 90 140 80 140 80 120 100 80 60 70 60 50 40 30 120 100 80 60 70 60 50 40 30 40 20 40 20 20 10 20 10 0 0 2 3 5 10 15 20 30 45 60 120 180 240 360 0 0 0 2 3 5 10 15 20 30 45 60 120 180 240 360 0 Time [min] Delta Reaction Time [ms] Delta Interstimulus Interval [ms] Figure 6-14: Correlation of midazolam serum concentration and outcome of CRTT performance (delta reaction time and delta Interstimulus interval), n=8. Katja Suter-Zimmermann Page 77 of 188 University of Basel, 2008
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TRANSMUCOSAL NASAL DRUG DELIVERY Sy
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Acknowledgments At the Hospital Pha
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Index EXPERIMENTAL SECTION 5 Projec
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Summary Summary Transmucosal nasal
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Summary Project III: In this random
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THEORETICAL SECTION
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1. Nasal drug delivery 1.2 Transmuc
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1. Nasal drug delivery 1.3 Challeng
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2. Impact of anatomy and physiology
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3. Midazolam 3 Midazolam 3.1 Physic
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Page 35 and 36: 3. Midazolam Administration of high
Page 37 and 38: 3. Midazolam gastrointestinal tract
Page 39 and 40: 4. Compounding of nasal midazolam p
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Page 106 and 107: 8 Overall discussion pharmacokineti
Page 108 and 109: 8 Overall discussion considered as
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Page 114 and 115: 10 Appendix 10.2 Project I 10.2.1 R
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Page 118 and 119: 10 Appendix 10.2.6 Specification: C
Page 120 and 121: 10 Appendix Katja Suter-Zimmermann
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10 Appendix Katja Suter-Zimmermann
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10 Appendix 10.3.2 Case report form
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10 Appendix Frequency 10.3.5 Intens
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10 Appendix 10.3.7 Serumconcentrati
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10 Appendix Identification midazola
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10 Appendix 10.3.8 Midazolam serum
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10 Appendix 10.3.10 Nasal delivery
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10 Appendix 10.4.3 Flowchart: multi
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11 References 11 References Abrams,
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11 References Erjefalt, J.S., I. Er
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11 References Irie, T. and K. Uekam
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11 References Malinovsky, J.M., C.
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11 References Scheepers, M., B. Sch
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12 Curriculum vitae 12 Curriculum v
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