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Pharmacokinetics of intravenous dantrolene in children
J Lerman1, M E McLeod, H A Strong
1Department of Anaesthesia, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Insights
Intravenous dantrolene at 2.4 mg/kg in children aged 2-7 years showed safe and predictable blood concentrations, similar to adults. The drug
Area of Science:
- Pediatric Pharmacology
- Pharmacokinetics
- Anesthesiology
Background:
- Dantrolene is a muscle relaxant used in various medical settings.
- Pharmacokinetic data for intravenous dantrolene in pediatric populations is limited.
- Understanding drug behavior in children is crucial for safe and effective treatment.
Purpose of the Study:
- To determine the pharmacokinetics of intravenous dantrolene and its metabolites in children.
- To compare pediatric dantrolene pharmacokinetics with existing adult data.
- To assess the safety and predictability of intravenous dantrolene dosing in pediatric patients.
Main Methods:
- Ten children aged 2-7 years received intravenous dantrolene (2.4 mg/kg) during elective surgery.
- Whole blood samples were collected at multiple time points post-infusion.
- Concentrations of dantrolene and its metabolites were quantified using high-performance liquid chromatography.
Main Results:
- Dantrolene concentrations peaked rapidly and then declined, with an elimination half-life of approximately 10 hours.
- A metabolite, 5-hydroxydantrolene, showed a delayed peak and a similar elimination half-life.
- The other measured metabolite was undetectable, and all children recovered without complications.
Conclusions:
- Intravenous dantrolene at 2.4 mg/kg yields safe and predictable blood concentrations in children.
- Pediatric pharmacokinetic profiles appear similar to those observed in adults.
- This study supports the use of intravenous dantrolene in pediatric surgical patients.
Abstract:
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.