Pharmacokinetics of intravenous dantrolene in children.
To determine the pharmacokinetics of iv dantrolene and its metabolites in children, ten children 2-7 yr of age scheduled for minor elective surgery, were studied. After induction of anesthesia and tracheal intubation, dantrolene (2.4 mg/kg) was administered iv over 10.2 +/- 0.83 min. Venous blood samples (3 ml) were obtained 1, 5, 10, 20, and 30 min and 1, 2, 4, 8, 12, and 20 h after the dantrolene infusion. Whole blood concentrations of dantrolene, 5-hydroxydantrolene, and nitroreduced acetylated dantrolene were measured by high-performance liquid chromatography. The whole blood concentration of dantrolene decreased rapidly from a mean (+/- SD) of 6.03 +/- 0.93 microgram/ml 1 min after the end of the dantrolene infusion to 3.56 +/- 0.49 microgram/ml at 1 h. Between 1 and 4 h, the concentration of dantrolene either remained constant or increased slightly. Thereafter, the concentration of dantrolene decreased slowly with an elimination half-life (mean +/- SD) of 10.0 +/- 2.6 h. The mean (+/- SD) time for the concentration of dantrolene to decrease to 3.0 micrograms/ml was 6.55 +/- 2.88 h. The whole blood concentration of 5-hydroxydantrolene reached a maximum of 0.60 +/- 0.18 microgram/ml approximately 7 h after the dantrolene and decreased thereafter with an elimination half-life of 9.0 +/- 2.5 h. The concentration of nitroreduced acetylated dantrolene was below the limit for detection at all times. All children recovered without complications. Intravenous dantrolene, 2.4 mg/kg, produces safe and predictable blood concentrations in children similar to those reported in adults.
Lerman
J
J
Department of Anaesthesia, Hospital for Sick Children, University of Toronto, Ontario, Canada.
McLeod
M E
ME
Strong
H A
HA
D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003620:Dantrolene / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D004198:Disease Susceptibility; D006801:Humans; D007262:Infusions, Intravenous; D008305:Malignant Hyperthermia / Q000517:prevention & control*
C034271:5-hydroxydantrolene; D003620:Dantrolene