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 MRI image quality The radiologists assessed the image quality of each MRI examination, according to following fivegrade scale: (1) excellent image quality (ideal image quality for diagnosis), (2) good image quality (very little motion artifacts), (3) satisfactory image quality (diagnosis possible, despite some motion artifacts), (4) poor image quality (diagnostic information is affected by motion artifacts), and very poor image quality (no diagnosis because of extensive motion artifacts). Local irritation and adverse drug reactions Radiologic technicians were instructed to register all spontaneous reports on local irritation and adverse effects. Patients were asked to classify the intensity of the local irritation (mild, intermediate, strong) and the time for recovery was noted. The radiologists were instructed to treat serious adverse reactions with flumazenil (Anexate ® ). Analysis and statistics Two tailed t-tests for differences in continuous variables and χ 2 -tests (image quality) of trends for ordinal variables were performed. Statistical significance was accepted for p
7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis 7.3 Results Study population Between May 2006 and February 2007, overall 110 patients were recruited and randomly assigned to either treatment (MD, n=56) or comparator group (UD, n=54). There were no significant differences between patients recruited in the study centers A, B, C, and D. Regarding age (MD 51 ± 16 years, UD 51 ± 13 years), weight (MD 72 ± 15 kg, UD 77 ± 16 kg) and sex (MD m18/f38, UD m19/f35) was no significant difference between treatment (MD) and comparator group (UD). The MRI examinations were classified into three groups: investigations of a limb (body and head outside of the MRI tunnel), investigation of head and neck (only head and neck inside the MR tunnel), and whole body investigations (whole body inside the MR tunnel). There was no significant difference between the classification of MRI examinations of treatment and comparator group. Table 7-1: Demographic and clinical characteristics of the study population (n=110). Characteristics Treatment group MD (n=56) Comparator group UD (n=54) Age, y (SD) 1 51 (16) 51 (13) Weight, kg (SD) 72 (15) 77(16) Sex (m/f) 18/38 19/35 VAS before 0.72 (0.23) 0.66 (0.25) Center A 15 15 Center B 13 12 Center C 13 12 Center D 15 15 Duration of MRI examination, min (SD) 31 (13) 3 31 (11) 4 Acquired sequences (SD) 7 (4) 3 6 (2) 4 Total body examination 41 3 37 4 Head/neck examination 12 3 12 4 Limb examination 3 3 3 4 Contrast agent, i.v. 14 3 7 4 Arthroscopy 2 14 3 11 4 1 a 16 year-old patient was enclosed, after her mother signed consent form. This protocol deviation was tolerated and the acquired data entered the final analysis 2 intra-articular injection of contrast agent 3 n=53, no data for therapy failures or dropout 4 n=52, no data for therapy failure and protocol deviation Additional dose and therapy failure All patients treated only with the initial dose of 1 mg midazolam (MD n=52, UD n=49) completed MRI examination. Additional administration of 1 mg midazolam (total administered dose of 2 mg) was required of total 17 patients (MD n=13, UD n=4). This additional midazolam dose was not judged as therapy failure, but if MRI examination was not possible or had to be interrupted the Katja Suter-Zimmermann Page 87 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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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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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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