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Pharmacokinetics of trimeprazine in children
S Sponheim1, H Aune, M Gulliksen
1Department of Anaesthesia, Rikshospitalet, Oslo, Norway.
Insights
This study investigated trimeprazine (alimemazine) pharmacokinetics in children, finding significant interindividual differences in drug levels and response. No trimeprazine was detected in cerebrospinal fluid, suggesting limited central nervous system penetration.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
Background:
- Trimeprazine (alimemazine) is used as a pre-anesthetic medication in children.
- Understanding its pharmacokinetic profile is crucial for optimizing therapeutic outcomes and minimizing adverse effects.
Purpose of the Study:
- To characterize the pharmacokinetics of trimeprazine following oral administration in pediatric patients.
- To assess the relationship between blood trimeprazine concentrations and pre-anesthetic sedation.
- To investigate the penetration of trimeprazine into the cerebrospinal fluid (CSF).
Main Methods:
- Pharmacokinetic analysis of trimeprazine in venous blood over 24 hours in six children after a 3 mg.kg-1 oral dose.
- Evaluation of pre-anesthetic sedation.
- Gas chromatography measurement of trimeprazine concentrations in CSF and blood in three additional children.
Main Results:
- Median peak blood trimeprazine concentration was 0.357 µmol/L at 1-2 hours post-ingestion.
- The estimated half-life was 6.8 hours, with a blood clearance of 3.7 L/kg/hr (assuming 100% bioavailability).
- No trimeprazine was detected in cerebrospinal fluid; a correlation was observed between sedation and blood concentrations, with substantial interindividual variability.
Conclusions:
- Trimeprazine exhibits significant interindividual pharmacokinetic variability in children.
- The lack of CSF detection suggests limited central nervous system penetration.
- Anticipated interindividual variations in drug response necessitate careful dosage monitoring despite standardized regimens.
Abstract:
The pharmacokinetics of trimeprazine (alimemazine) were studied over 24 hr in six children after a recommended preanaesthetic oral dose of 3 mg.kg-1. The degree of sedation before anaesthesia was evaluated. Median maximal venous blood drug concentration was 0.357 mumols.1(-1), 1-2 hr after oral ingestion, half-life 6.8 hr and AUC0-infinity h 2.758 mumols.1(-1) hr. Assuming 100 per cent bioavailability, blood clearance was estimated to median 3.7 1.kg-1.hr-1. Trimeprazine concentrations in cerebrospinal fluid (CSF) and in venous blood were compared in three other children, measured by gas chromatography. No trimeprazine was detected in the cerebrospinal fluid. We found a rough correlation between preanaesthetic sedation and blood trimeprazine concentrations. The kinetic parameters showed substantial interindividual differences, and accordingly, major interindividual variations in drug response might be anticipated even on standardized dosage regimens.