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Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration
B V Murthy1, K S Pandya, P D Booker
1Royal Liverpool Children's NHS Trust, UK.
Insights
Pediatric pharmacokinetics of tramadol show similar intravenous (IV) and extensive systemic absorption after caudal epidural administration in children undergoing surgery. O-demethyl tramadol metabolite levels were lower after caudal epidural administration.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
- Pain Management
Background:
- Tramadol is a widely used analgesic in pediatric patients.
- Understanding its pharmacokinetic profile is crucial for safe and effective pain management.
- Previous studies have established tramadol pharmacokinetics in adults, but data in children are less extensive.
Purpose of the Study:
- To investigate and compare the pharmacokinetics of tramadol following intravenous (IV) and caudal epidural administration in children.
- To evaluate the systemic absorption and metabolite profiles of tramadol in pediatric surgical patients.
Main Methods:
- A single bolus dose of tramadol (2 mg/kg) was administered intravenously (n=9) or via caudal epidural injection (n=5) to healthy children (1-12 years) undergoing surgery.
- Serum concentrations of tramadol and its metabolite O-demethyl tramadol (MI) were measured up to 20 hours post-administration.
- Pharmacokinetic variables were analyzed using a non-compartmental model and gas chromatography.
Main Results:
- After IV administration, mean elimination half-life was 6.4 h, volume of distribution 3.1 L/kg, and total plasma clearance 6.1 mL/kg/min.
- After caudal epidural administration, mean elimination half-life was 3.7 h, volume of distribution 2.0 L/kg, and total clearance 6.6 mL/kg/min.
- The AUC quotient confirmed extensive systemic absorption of tramadol after caudal epidural administration, with lower MI serum concentrations compared to IV administration.
Conclusions:
- Tramadol exhibits similar pharmacokinetic profiles after IV and caudal epidural administration in children aged 1-12 years.
- Caudal epidural administration leads to extensive systemic absorption of tramadol.
- These findings support the use of caudal epidural tramadol for effective pain management in pediatric surgery.
Abstract:
We have studied the pharmacokinetics of a single bolus dose of tramadol 2 mg kg-1 injected either i.v. or into the caudal epidural space in 14 healthy children, aged 1-12 yr, undergoing elective limb, urogenital or thoracic surgery. Serum concentrations of tramadol and its metabolite O-demethyl tramadol (MI) were measured in venous blood samples at various intervals up to 20 h by non-stereoselective gas chromatography with nitrogen-selective detection. All pharmacokinetic variables were evaluated using a non-compartmental model. After a single i.v. injection (n = 9), the mean elimination half-life of tramadol was 6.4 (SD 2.7) h, with a volume of distribution of 3.1 (1.1) litre kg-1 and total plasma clearance of 6.1 (2.5) ml kg-1 min-1. All of these pharmacokinetic variables were similar to those reported previously in adults. After caudal epidural administration (n = 5), mean elimination half-life was 3.7 (0.9) h, volume of distribution was 2.0 (0.4) litre kg-1 and total clearance was 6.6 (1.9) ml kg-1 min-1. The caudal/i.v. quotient of the AUC was 0.83, which confirms that there is extensive systemic absorption of tramadol after caudal administration. Serum concentrations of MI showed a time course typical of a metabolite after both modes of administration. Serum concentrations of MI after caudal administration were lower than those after i.v. injection.