Pharmacokinetics and pharmacodynamics of intranasal remimazolam-a randomized controlled clinical trial
| Autor: | Robert Saunders, Martin Donsbach, Lyn Webster, Marija Pesic, Frank Schippers, Thomas Stoehr |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.drug_class Sedation Cmax 03 medical and health sciences Route of administration Benzodiazepines Young Adult 0302 clinical medicine Intranasal bioavailability Pharmacokinetics Double-Blind Method 030202 anesthesiology Memory 0502 economics and business medicine Reaction Time Humans Hypnotics and Sedatives Pharmacology (medical) Administration Intranasal Remimazolam Pharmacology Cross-Over Studies business.industry 05 social sciences General Medicine Pharmacodynamics Sedative Anesthesia 050211 marketing Nasal administration medicine.symptom business |
| Zdroj: | European Journal of Clinical Pharmacology |
| ISSN: | 1432-1041 |
| Popis: | Purpose Remimazolam is a novel and ultra-short-acting sedative currently developed for intravenous use in procedural sedation, general anesthesia, and ICU sedation. However, intravenous administration is not always appropriate, depending on the patient or setting. This study evaluated intranasal administration as a potential alternative route. Methods The study used a randomized, double-blind, 9 period cross-over design to compare the pharmacokinetics, pharmacodynamics, and safety of single intranasal doses of 10, 20, and 40 mg remimazolam (as powder or solution) with intranasal placebo and 4 mg intravenous remimazolam. Results Intranasal remimazolam powder had a consistent absolute bioavailability of approximately 50%; Tmax was 10 min; AUC and Cmax were dose-proportional. The higher doses of intranasal solution, however, resulted in decreasing bioavailability and loss of dose-proportionality in AUC and Cmax despite complete drug absorption due to partial swallowing of dose and the resulting first-pass effect. Pharmacodynamics were generally consistent with PK. Peak effects (drowsiness, relaxation, any, memory, response time) were in similar ranges after intranasal (10 to 40 mg) as intravenous (4 mg) dosing and were partially, but not consistently, dose-related. Safety results were generally consistent with other benzodiazepines; however, intranasal remimazolam (but not placebo) caused nasal discomfort/pain, in some cases even severe. Conclusions Intranasal administration of remimazolam was safe and caused sedative effects. However, the severe pain and discomfort caused by intranasal remimazolam prohibit its use by this route of administration, at least with the currently available intravenous formulation. |
| Databáze: | OpenAIRE |
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