Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...
Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...
Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...
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6. Project II: Pharmacokinetic <strong>of</strong> transmucosal nasal delivered midazolam – impact <strong>of</strong> adjuvants<br />
midazolam) decreased within 5 minutes after administration (very slight to slight) and 15 minutes<br />
after administration <strong>of</strong> Preparation 3 only one volunteer indicated very slight nasal irritation.<br />
Irritation in the throat after administration <strong>of</strong> Preparation 1, 2, and 3 (nasal delivery <strong>of</strong> 1 mg<br />
midazolam) was never rated as strong immediately after administration (very slight, slight or<br />
intermediate). Irritation in the throat was once described as strong (scratching in the throat)<br />
15 minutes after administration <strong>of</strong> Preparation 3. Generally, 15 minutes after nasal administration <strong>of</strong><br />
1 mg midazolam local irritation has almost disappeared and later (30 minutes and 4h) volunteers<br />
indicated no local irritation at all. <strong>Nasal</strong> irritation after administration <strong>of</strong> Preparation 4 and 5 (nasal<br />
delivery <strong>of</strong> 3 mg midazolam) decreased within 15 minutes after administration (very slight to slight)<br />
and lasted until 30 minutes after administration <strong>of</strong> Preparation 4. Preparation 5 caused more<br />
irritation in the throat area which lasted until 30 minutes after nasal administration. Four hours after<br />
nasal administration <strong>of</strong> study medication no local irritation was left.<br />
Some subjects complained about teary eyes<br />
number <strong>of</strong> volunteers with watery eyes after<br />
midazolam administration<br />
6<br />
5<br />
4<br />
3<br />
2<br />
1<br />
0<br />
5<br />
3<br />
2 2<br />
1<br />
P1 P2 P3 P4 P5<br />
(see Figure 6-5), bitter or unpleasant taste, or<br />
nasal prickling immediately after nasal<br />
administration <strong>of</strong> study medication. Onesided<br />
nasal administration <strong>of</strong> midazolam<br />
(Preparation 3, 4, and 5) caused teary eye<br />
only on the side <strong>of</strong> administration.<br />
No relevant changes in blood pressure, heart<br />
rate, and oxygen saturation were observed<br />
after i.v. and nasal administration <strong>of</strong><br />
midazolam (1 mg and 3 mg).<br />
Figure 6-5: Teary eyes after nasal administration<br />
<strong>of</strong> Preparation 1 to 5 (P1, P2, P3, P4, and P5) to<br />
8 Volunteers (n=8) rated. One-sided nasal<br />
administration (P3, P4, and P5) caused teary eye<br />
only on the side <strong>of</strong> administration.<br />
Katja Suter-Zimmermann Page 67 <strong>of</strong> 188 University <strong>of</strong> Basel, 2008
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