Abstract
Aim
To investigate total serum levobupivacaine concentrations after a caudal‐epidural loading dose followed by a maintenance infusion in infants aged 3‐6 months over 48 hours.
Background
The local anaesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modelling with racemic bupivacaine. This study will inform clinical practice in this age group and validate the pharmacokinetic model for levobupivacaine infusions in infants, aged 3‐6months.
Methods
The clinical trial was conducted in 8 infants aged 3‐6 months, undergoing bladder exstrophy repair. Pharmacokinetic modelling allowed optimisation of clinical sampling to measure total levobupivacaine and α1‐acid glycoprotein and prediction of the effect of α1‐acid glycoprotein on levobupivacaine plasma protein binding.
Results
The observed median total levobupivacaine serum concentration was 0.30 mg.L−1 (range: 0.20‐0.70 mg.L−1) at 1 hour after the loading dose of 2 mg.kg−1. The median total levobupivacaine concentration after 47 hours of infusion, at 0.2 mg.h−1.kg−1, was 1.21 mg.L−1 (0.07‐1.85 mg.L−1). Concentrations of α1‐acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modelling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03 mg.L−1.
Conclusion
This study examines the pharmacokinetics of levobupivacaine after a loading dose (given over 5 minutes) followed by a maintenance infusion in infants 3‐6 months. The study allows the development of a pharmacokinetic model, combining levobupivacaine and α1‐acid glycoprotein data. Modelling indicates that unbound levobupivacaine quickly reaches steady state once the infusion is started. Simulations suggest that it may be possible to continue the infusion beyond 48 hours.
To investigate total serum levobupivacaine concentrations after a caudal‐epidural loading dose followed by a maintenance infusion in infants aged 3‐6 months over 48 hours.
Background
The local anaesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modelling with racemic bupivacaine. This study will inform clinical practice in this age group and validate the pharmacokinetic model for levobupivacaine infusions in infants, aged 3‐6months.
Methods
The clinical trial was conducted in 8 infants aged 3‐6 months, undergoing bladder exstrophy repair. Pharmacokinetic modelling allowed optimisation of clinical sampling to measure total levobupivacaine and α1‐acid glycoprotein and prediction of the effect of α1‐acid glycoprotein on levobupivacaine plasma protein binding.
Results
The observed median total levobupivacaine serum concentration was 0.30 mg.L−1 (range: 0.20‐0.70 mg.L−1) at 1 hour after the loading dose of 2 mg.kg−1. The median total levobupivacaine concentration after 47 hours of infusion, at 0.2 mg.h−1.kg−1, was 1.21 mg.L−1 (0.07‐1.85 mg.L−1). Concentrations of α1‐acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modelling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03 mg.L−1.
Conclusion
This study examines the pharmacokinetics of levobupivacaine after a loading dose (given over 5 minutes) followed by a maintenance infusion in infants 3‐6 months. The study allows the development of a pharmacokinetic model, combining levobupivacaine and α1‐acid glycoprotein data. Modelling indicates that unbound levobupivacaine quickly reaches steady state once the infusion is started. Simulations suggest that it may be possible to continue the infusion beyond 48 hours.
| Original language | English |
|---|---|
| Pages (from-to) | 161-168 |
| Number of pages | 8 |
| Journal | Pediatric Anesthesia |
| Volume | 29 |
| Issue number | 2 |
| Early online date | 17 Nov 2018 |
| DOIs | |
| Publication status | Published - 1 Feb 2019 |
Keywords
- bladder exstrophy
- caudal-epidural infusion
- infants
- levobupivacaine
- pharmacokinetics
- α -acid glycoprotein