• Rita Vashisht, Anju A Bendon, Ijeoma Okonkwo, Davandra Patel, Catherine Fullwood, Kayode Ogungbenro, Leon Aarons, and Adam S Darwich.
• Department of Paediatric Anaesthesia, Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital, Manchester, UK.
• Paediatr Anaesth. 2019 Feb 1; 29 (2): 161-168.

BackgroundThe local anesthetic, levobupivacaine, is the safer enantiomer of racemic bupivacaine. Present protocols for levobupivacaine are based on studies and pharmacokinetic modeling with racemic bupivacaine.AimsThe aim is to investigate total serum levobupivacaine concentrations after a caudalepidural loading dose followed by a maintenance infusion over 48 hours in infants aged 3-6 months.MethodsThe clinical trial was conducted in eight infants aged 3-6 months, undergoing bladder exstrophy repair. Pharmacokinetic modeling allowed optimization 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.ResultsThe observed median total levobupivacaine serum concentration was 0.30 mg/L (range: 0.20-0.70 mg/L) at 1 hour after the loading dose of 2 mg/kg. The median total levobupivacaine concentration after 47 hours of infusion, at 0.2 mg/kg/h, was 1.21 mg/L (0.07-1.85 mg/L). Concentrations of α1 -acid glycoprotein were found to rise throughout the study period. Pharmacokinetic modeling suggested that unbound levobupivacaine quickly reached steady state at a concentration of approximately 0.03 mg/L.ConclusionThe study allows the development of a pharmacokinetic model, combining levobupivacaine and α1 -acid glycoprotein data. Modeling 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.© 2018 John Wiley & Sons Ltd.

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