Pharmacokinetics and pharmacodynamics of a new highly concentrated intranasal midazolam formulation for conscious sedation

Schrier, Lenneke; Zuiker, Rob; Merkus, F. W. H. M.; Klaassen, Erica S.; Zheng, Guoyan; Tuk, B.; Gerven, Joop M. A. van; Geest, Ronald van der; Groeneveld, Geert Jan

doi:10.1111/bcp.13163

Cited by 21 publications

(23 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this trial, the dose of midazolam differed in the KMIN and KMO groups. Midazolam doses of 0.5 mg/kg for the oral route and 0.2 mg/kg for the intranasal route are in agreement with previous studies [17], and supported by the fact that the bioavailability of the nasal route is more than twice of the oral route (75% vs. 36%) [35,36]. Intranasal use of doses greater than 0.2 mg/kg causes excessive coughing and sneezing with greater expulsion of the drug [18], while doses of 0.5 mg/kg of oral midazolam provide good sedation [20].…”

Section: Discussionsupporting

confidence: 89%

Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation

et al. 2019

View full text Add to dashboard Cite

PurposeThe optimal sedative regime that provides the greatest comfort and the lowest risk for procedural sedation in young children remains to be determined. The aim of this randomized, blinded, controlled, parallel-design trial was to evaluate the efficacy of intranasal ketamine and midazolam as the main component of the behavioral guidance approach for preschoolers during dental treatment.Materials and methodsChildren under seven years of age, with caries and non-cooperative behavior, were randomized into three groups: (KMIN) intranasal ketamine and midazolam; (KMO) oral ketamine and midazolam; or (MO) oral midazolam. The dental sedation appointments were videotaped, and the videos were analyzed using the Ohio State University Behavioral Rating Scale (OSUBRS) to determine the success of the sedation in each group. Intra- and postoperative adverse events were recorded. Data analysis involved descriptive statistics and non-parametric tests (P < 0.05, IBM SPSS).ResultsParticipants were 84 children (28 per group; 43 boys), with a mean age of 3.1 years (SD 1.2). Children’s baseline and the dental sedation session characteristics were balanced among groups. The success of the treatment as assessed by the dichotomous variable ‘quiet behavior for at least 60% of the session length’ was: KMIN 50.0% (n = 14; OR 2.10, 95% CI 0.71 to 6.30), KMO 46.4% (n = 13; OR 1.80, 95% CI 0.62 to 5.40), MO 32.1% (n = 9) (P = 0.360). Adverse events were minor, occurred in 37 of 84 children (44.0%), and did not differ among groups (P = 0.462).ConclusionAll three regimens provided moderate dental sedation with minor adverse events, with marked variability in the behavior of children during dental treatment. The potential benefit of the ketamine–midazolam combination should be further investigated in studies with larger samples.Trial registrationClinicalTrials.gov, identifier: NCT02447289. Registered on 11 May 2015, named “Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO).”

show abstract

Section: Discussionsupporting

confidence: 89%

Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Population average PK with identified PD model Pharmacokinetic studies that require collection of multiple blood samples are challenging, particularly so in children. Consequently, it can be practically infeasible to obtain more than a limited number of samples for each individual [Rigby-Jones and Sneyd, 2012]. Several studies of pharmacodynamics in children have therefore used predicted plasma concentrations, for example [Rigouzzo et al, 2010;Jeleazcov et al, 2008], solving the ethical and practical issues related to blood sampling, and reducing cost by omitting drug assays [Rigby-Jones and Sneyd, 2012].…”

Section: Models From Clinical Pharmacology With Identified Nonlinearitymentioning

confidence: 99%

Models for control of intravenous anesthesia

Soltesz

Heusden

Dumont

2020

Automated Drug Delivery in Anesthesia

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…In humans, both MDZ and DZP can be effective and potent via IN delivery [ 80 , 152 – 154 ]. When compared, DZP is more lipophilic than MDZ, which can result in DZP’s better absorption by the nasal mucosa and potentially higher brain concentration [ 80 , 152 , 154 ]. However, DZP’s high lipophilicity also causes the drug to be rapidly redistributed into peripheral tissues which eventually results in DZP’s decreased concentration in the brain [ 80 , 152 ].…”

Section: Introductionmentioning

confidence: 99%

First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines

et al. 2021

View full text Add to dashboard Cite

Status epilepticus (SE) or prolonged epileptic seizure activity is a common neurological emergency with a high mortality rate and, if left untreated, can lead to irreversible cerebral damage and systemic complications. Fast and effective first-line management is of paramount importance, particularly in the at-home management of seizures where drug administration routes are limited. Benzodiazepines (BZDs) have been exclusively used in veterinary medicine for decades as first-line drugs based on their high potency and rapid onset of action. Various administration routes exist in dogs, such as oral, intravenous, intramuscular, rectal, and intranasal, all with different advantages and limitations. Recently, intranasal drug delivery has become more popular due to its unique and favourable characteristics, providing potential advantages over other routes of drug administration in the management of canine SE. This narrative review provides an outline of the management of SE at home and in a hospital setting, discusses considerations and challenges of the various routes of BZD administration, and evaluates the impact of intranasal drug administration (nose-brain pathway) for controlling canine SE at home and within hospital settings.

show abstract

Pharmacokinetics and pharmacodynamics of a new highly concentrated intranasal midazolam formulation for conscious sedation

Cited by 21 publications

References 62 publications

Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation

Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation

Models for control of intravenous anesthesia

First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines

Contact Info

Product

Resources

About