Population pharmacokinetics of   - XXXX in adolescents undergoing posterior spinal fusion surgery.

@entity1 @entity190 @entity1009 @entity1635 @entity929 @entity2112
BACKGROUND: Despite demonstrated efficacy of   - @entity929 (EACA) in reducing @entity190 in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations. METHODS: Twenty @entity1 ages 12-17 years were enrolled, with 10 @entity1 in each of two groups based on diagnosis ( @entity2112 or @entity2112 ). Previously reported data from @entity1 undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics. RESULTS: Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical @entity1 were a plasma clearance of 153 ml @entity1009 ) 70 kg(-1) (6.32 ml @entity1009 ) kg(-0.75)), intercompartmental clearance of 200 ml @entity1009 ) 70 kg(-1) (8.26 ml @entity1009 ) kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23 litre kg(-1)). @entity1635 aetiology did not have a clinically significant effect on drug pharmacokinetics. CONCLUSIONS: The following dosing schemes are recommended according to @entity1 weight: weight <25 kg, 100 mg kg(-1) loading dose and 40 mg kg(-1) h(-1) infusion; weight  <=25 kg-<50 kg, 100 mg kg(-1) loading dose and 35 mg kg(-1) h(-1) infusion; and weight >= 50 kg, 100 mg kg(-1) loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this dosing strategy is warranted. CLINICAL TRIAL REGISTRATION: NCT01408823.
