Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

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7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis therapy was declared as failed. Overall, therapy failed in 3 patients (MD n=2, UD n=1). All therapy failures occurred within patients receiving 2 mg midazolam. Acquired data of one patient of the treatment group was excluded from final analysis, because of protocol deviation (after nasal administration of 1 mg midazolam the patient has withdrawn his consent and desired intravenous anxiolysis). Due to protocol deviation (application of false medication) one patient of comparator group had to be excluded from final analysis. Final analysis was performed with data acquired from 105 patients, completing MRI examination (MD n=53, UD n=52). Figure 7-2 displays the number of enrolled, randomized, and excluded patients. Included (n=110) (A: 30, B:25, C:25, D: 30) Randomized (n=110) Treatment, MD (n=56) Comparator, UD (n=54) VAS before VAS before Dropout (n=1) i.v. anxiolysis Therapy failure (n=1) MRI not possible 1mg midazolam nasal (MD, n=56) +1mg midazolam (n=13) 1mg midazolam nasal (UD, n=54) +1mg midazolam (n=4) Protocol deviation (n=1) Therapy failure (n=1) MRI not possible Therapy failure (n=1) MRI stopped MRI examination (n=12) MRI examination (n=42) MRI examination (n=49) MRI examination (n=3) MRI completed (n=11) MRI completed (n=42) MRI completed (n=49) MRI completed (n=3) - VAS after - Assessmet RT - Image quality - VAS after - Assessmet RT - Image quality - VAS after - Assessmet RT - Image quality - VAS after - Assessmet RT - Image quality Final analysis (n=53) Final analysis (n=52) Figure 7-2: Flow diagram of subject process through randomized study – evaluation of two preparations for nasal delivery of low-dose midazolam; enrolled n=110 (center A: 30, B: 25, C: 25, and D: 30); randomized n=110 (MD n=56, UD n=54); dropout n=1 (MD); protocol deviation n=1 (UD); therapy failure n=3 (MD n=2, UD n=1); additional dose n=17 (MD n=13, UD n=4); MRI completed n=105 (MD n=53, UD n=52), and final analysis n=105 (MD n=53, UD n=52). MD: multidose nasal spray (treatment), UD: unit dose nasal spray (comparator), VAS before/after: Visual analog scale before and after MRI examination, RT: radiologic technician. Katja Suter-Zimmermann Page 88 of 188 University of Basel, 2008
7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis Patient experience and anxiety reduction VAS [mm] 100 90 80 70 60 50 40 30 20 10 0 VASb VASa VASb VASa MD (n=53) n.s * * UD (n=52) VASb 71.1 64.9 VASa 23.0 24.2 Figure 7-3: Reduction of anxiety in treatment (MD, n=53) and comparator group (UD, n=52). For both groups anxiety score assessed before medication was significant higher than score assessed after MRI examination. There was no difference in anxiety reduction between the two groups. VASb: VAS before, VASa: VAS after, ( *): significant (p0.05), Anxiety score of all patients, who completed the MRI examination (n=105), are displayed in Figure 7-3. Between treatment and comparator group, there was no significant difference in anxiety score assessed before midazolam administration (VAS before ). In both groups (MD and UD) reduction of anxiety (VAS before -VAS after ) was significant (p
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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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3. Midazolam 3.2.1 Indications and
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3. Midazolam Administration of high
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3. Midazolam gastrointestinal tract
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4. Compounding of nasal midazolam p
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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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