Intravenous Lecithin-Coated Microcrystals of Dantrolene Are Effective in the Treatment of Malignant Hyperthermia

Karan, Steven M.; Lojeski, Edwin W.; Haynes, Duncan H.; Bina, Saiid; Wesche, David; Boedeker, Ben H.; Muldoon, Sheila M.

doi:10.1097/00132586-199704000-00062

Cited by 5 publications

(6 citation statements)

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“…Dantrolene was selected as a specific BCRP substrate based on data from in vitro and in vivo literature (Enokizono et al, 2008;Kodaira et al, 2010;Xiao et al, 2012). Both [ 14 C]WEB 2086 and dantrolene are known to exhibit a short mean residence time (MRT) in rats: MRT of WEB 2086 is 0.44 hour (V. Haeselbarth, G. Schoenfels, and H. Foerster, unpublished data), and MRT of dantrolene was reported to be 0.52 hour by Meyler et al (1979) and 3.1 hours by Karan et al (1996). Thus, it was expected that close to steady-state conditions would be achieved after a combined intravenous infusion of [ 14 C]WEB 2086 and dantrolene for 2 hours, enabling the function of both brain efflux transporters to be assessed in the s This article has supplemental material available at dmd.aspetjournals.org.…”

Section: Introductionmentioning

confidence: 99%

Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-Glycoprotein) and Bcrp Knockout Rats

et al. 2014

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Transporter gene knockout rat models are attracting increasing interest for mechanistic studies of new drugs as transporter substrates or inhibitors in vivo. However, limited data are available on the functional validity of such models at the blood-brain barrier. Therefore, the present study evaluated Mdr1a [P-glycoprotein (P-gp)], Bcrp, and combined Mdr1a/Bcrp knockout rat strains for the influence of P-gp and breast cancer resistance protein (BCRP) transport proteins on brain penetration of the selective test substrates [ .5-fold in double Mdr1a/Bcrp knockouts, and 7.3-fold in zosuquidar-treated wild-type rats, but was unchanged in Bcrp knockout rats. Mean BPR of dantrolene increased 3.3-fold in Bcrp knockouts and 3.9-fold in double Mdr1a/Bcrp knockouts compared with wild type, but was unchanged in the Mdr1a knockouts. The human intestinal CaCo-2 cell bidirectional transport system in vitro confirmed the in vivo finding that [ 14 C]WEB 2086 is a substrate of P-gp but not of BCRP. Therefore, Mdr1a, Bcrp, and combined Mdr1a/Bcrp knockout rats provide functional absence of these efflux transporters at the blood-brain barrier and are a suitable model for mechanistic studies on the brain penetration of drug candidates.

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Section: Introductionmentioning

confidence: 99%

Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-Glycoprotein) and Bcrp Knockout Rats

et al. 2014

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“…Nanosuspensions receiving groups did not indicated any gross native tissue destruction or systemic toxicity [17]. Karan et al, (1996) studied treatment of malignant hyperthermia using Phospholipid-coated nanosuspensions of dantrolene and sodium dantrolene. Particulate size range between 300 -800 nm for nanosuspension of sodium dantrolene and 500 -800 nm for nanosuspension of dantrolene were determined.…”

Section: Nanosuspensionmentioning

confidence: 99%

“…Due to drug dosing near plateau effect, ED95 became more significant. In swine models, malignant hyperthermia was treated magnificently with nanosuspensions [18]. Ward and Yalkowski (1993) revealed that due to matched speed of injection with blood flow rate lead to arisen of plug flow.…”

Section: Nanosuspensionmentioning

confidence: 99%

A Review about various Nanomaterials in Drug Delivery Systems and their Applications

Brahamdutt¹,

Arun²,

Sangwan³

et al. 2018

IJRDPL

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Most of drug entities face the problems like reduced absorption, faster metabolism and elimination, toxicity because of drug distribution to other tissues, low drug solubility, unpredictable bioavailability, etc. These issues need to be work out so as to make the novel drug delivery systems for successful therapy. Use of nanotechnology is one of the promising strategies to overcome all of these problems. Distinctive properties of nanomaterials like smaller particles size, high surface area, and ease of suspending in liquids, deeper access across the cells and organelles, flexib le optical and magnetic properties are offered by nanoparticles as compared to other micro or macro sized particles. Nanomaterials can be classified into different categories based on their drug delivery system, dimensions, structure and consistency. Various types of nano-formulations (such as nanoparticles, nano-suspension, liposomes, hydrogels, solid lipid nanoparticles, dendrimers, microneedles, ocular insert/disk, transcorneal iontophoresis) have been used by the researchers for modulating the physicochemical properties and biological activities of the drugs. This review highlights the various types of nanomaterials with their advantages and applications in the pharmaceuticals for enhanced physicochemical properties and better biological activities with reduced toxicity and higher biocompatibility .

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“…Dantrolene has a pH value of 9.5 and is a highdegree alkaline. Therefore, it should be diluted with 60 ml of water before use (Karan et al, 1996;Schneiderbanger et al, 2014). Heating the solution to 40oC beforehand enables the powder to dissolve.…”

Section: Treatmentmentioning

confidence: 99%

Malignant hyperthermia in dogs during general anaesthesia

Güzel

Mckinstry²

2017

Journal of Istanbul Veterinary Sciences

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Malignant hyperthermia is a pharmacogenetic disorder of skeletal muscles developing as a hypermetabolic response to inhalation anaesthetics such as halothane, sevoflurane or isoflurane and depolarizing muscle relaxants such as succinylcholine. It is produced by mutation of the RYR1 gene in dogs. In anaesthetised dogs, regardless of the anaesthetic drugs used, calcium ion channel activity may change and malignant hyperthermia may develop. Clinical features are hyperthermia, tachypne, hypercarbia, increased oxygen consumption, severe metabolic acidosis, hyperkalemia, cardiac arrhytmias and muscle rigidity. For a diagnosis of malignant hyperthermia to be made, at least 3 of the clinical findings must be determined. Dantrolene sodium is specific antagonist of malignant hyperthermia. However, it is not usually preferred by veterinary practitioners due to its high cost as well as the low incidence of the occurrence of this complication. Therefore it is useful for alternative drugs such as acepromazine, diazepam and alfentanil to be used for the treatment of clinical findings manifested during malignant hyperthermia. The purpose of this review is to share with colleagues the latest information regarding the treatment of canine malignant hyperthermia occurring in relation to general anaesthesia

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Intravenous Lecithin-Coated Microcrystals of Dantrolene Are Effective in the Treatment of Malignant Hyperthermia

Cited by 5 publications

References 0 publications

Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-Glycoprotein) and Bcrp Knockout Rats

Brain Penetration of WEB 2086 (Apafant) and Dantrolene in Mdr1a (P-Glycoprotein) and Bcrp Knockout Rats

A Review about various Nanomaterials in Drug Delivery Systems and their Applications

Malignant hyperthermia in dogs during general anaesthesia

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