Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: An investigation in rats, dogs, and swine

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

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Dantrolene effectively treats malignant hyperthermia (MH) but the current form, Dantrium®, must be dissolved to a 0.33 mg/mL, pH 9.5 solution. This study describes lecithin-coated microcrystal formulations of sodium dantrolene (MC-NaD) and neutral dantrolene (MC-D) which reconstitute to 200 mg/mL within 1 min. In rats, the pharmacokinetics and pharmacodynamics of MC- NaD and Dantrium® were similar: half-lives of 3.1 h, volume of distributions of 0.54 and 0.59 L/kg, and 95% effective dose (ED95) values for depression of skeletal muscle twitch height (ED95T) of 2.6 ± 0.7 and 2.8 ± 0.5 mg/kg. In swine, the ED95T values for MC-NaD and Dantrium® were also similar (2.8 ± 0.4 vs 2.7 ± 0.6 mg/kg), but MC-D and Dantrium® were only similar at doses more than 2.5 mg/kg (ED95T: 3.5 ± 0.4 vs 2.7 ± 0.5 mg/kg). In susceptible swine, MC-NaD successfully treated five of six MH episodes and prevented MH in three of four swine. However, MC-NaD caused marked pulmonary hypertension in swine, while MC-D caused only a mild response that was eliminated by filtration. Likewise, MC-D caused no pulmonary response in dogs. These observations suggest that MC-D has potential to improve the treatment of MH.

Original languageEnglish (US)
Pages (from-to)796-802
Number of pages7
JournalAnesthesia and analgesia
Volume82
Issue number4
DOIs
StatePublished - Apr 19 1996
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Intravenous lecithin-coated microcrystals of dantrolene are effective in the treatment of malignant hyperthermia: An investigation in rats, dogs, and swine'. Together they form a unique fingerprint.

  • Cite this