Dantrolene
Dantrolene. Skeletal muscle relaxant acting at the ryanodine receptor — inhibits sarcoplasmic Ca²⁺ release. First-line for malignant hyperthermia… Oral half-life 10 h.
Skeletal muscle relaxant acting at the ryanodine receptor — inhibits sarcoplasmic Ca²⁺ release. First-line for malignant hyperthermia (rapid IV reversal); chronic oral use for spasticity in MS / spinal cord injury / cerebral palsy. Hepatotoxicity at chronic use.
PK: the route-split half-life is resolved in favour of the intravenous value. The stored oral 15 h is absorption rate-limited and appears nowhere in its cited paper, which states no pharmacokinetic parameter at all; the oral 15.8 h that does exist elsewhere is attributed by its own authors to "continued absorption of dantrolene in the postoperative period". Adults and children agree on 10 h, so one disposition value serves both routes — though the verbatim source for it is a PAEDIATRIC study (children aged 2 to 7), which also condemns the stored 56 L, a volume physiologically impossible for a small child. The adult figure is 26.1 L, the sum of the two compartment volumes in Podranski 2005 (PMID:16301243), flagged as arithmetic rather than a quoted total. F 0.7 IS DELETED WITHOUT REPLACEMENT: no human absolute bioavailability exists in any species-appropriate abstract — the only absolute figure found anywhere is 39% in HORSES. The old citation is retained as a PHARMACODYNAMIC reference, since it does support one thing: plasma and effect correlate in healthy volunteers but "No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients".
Pharmacokinetics
- Oral — t½ 10 h · Vd 26.1 L
- IV — t½ 10 h · F 100% · Vd 26.1 L
Sources: PMID:499321, PMID:2929999, PMID:16301243, PMID:3057938