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

Abstract:

:Dantrolene effectively treats malignant hyperthermia (MH) hut 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 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.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Karan SM,Lojeski EW,Haynes DH,Bina S,Wesche DL,Boedeker BH,Muldoon SM

doi

10.1097/00000539-199604000-00021

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

796-802

issue

4

eissn

0003-2999

issn

1526-7598

journal_volume

82

pub_type

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