Population Pharmacokinetic Study of Amoxicillin-treated Burn Patients Hospitalized at a Tertiary Swiss Centre [PublishAheadOfPrint]

Objectives: To investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens.

Methods: Prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analysed using non-linear mixed effects modelling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the minimal inhibitory concentration (fT>MIC).

Results: A two-compartment model best described the data. Creatinine clearance (CL_CR) and body weight (BW) influenced amoxicillin CL and central volume of distribution (V1), respectively. The median CL_CR (Cockcroft-Gault formula) was high (128 mL/min) with 25% of patients having CL_CR > 150 mL/min. The CL, V1 and t_1/2 values at steady-state for a patient with a CL_CR of 110 mL/min and BW of 70 kg were 13.6 L/h, 9.7 L and 0.8 h, respectively. Simulations showed that a target fT>MIC ≥ 50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1-2 g q6-8 h) when the MIC was low (< 1 mg/L). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CL_R or higher MIC. Prolonging amoxicillin infusion from 30 min to 2 h had a favourable effect on target attainment.

Conclusion: This population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with non-burn patients. Situations of augmented CL_CR and/or high bacterial MIC target values may require dosage increases and longer infusion durations.

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