Impact of high-flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy

International Journal of Antimicrobial Agents
Katrina HuiCarl M J Kirkpatrick

Abstract

Clearance of small molecules such as amoxicillin and clavulanic acid is expected to increase during high-flux haemodialysis, which may result in lower concentrations and thus reduced efficacy. To date, clearance of amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely unexplored. Using published pharmacokinetic parameters, a two-compartment model with first-order input was simulated to investigate the impact of high-flux haemodialysis on the probability of target attainment (PTA) of orally administered AMC combination therapy. The following pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For amoxicillin, the time that the free concentration remains above the minimum inhibitory concentration (MIC) of ≥50% of the dosing period (≥50%ƒT>MIC) was used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of ≥45% of the dosing period (≥45%ƒT>0.1 mg/L) was used. Dialysis clearance reported in low-flux haemodialysis for both compounds was doubled to represent the likely clearance during high-flux haemodialysis. Monte Carlo simulations were performed to produce concentration-time profiles over 10 days in 1000 virtual patients. Seven different regimens commonly seen in...Continue Reading

Citations

Jul 18, 2017·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Kalsea J Koss, Megan R Gunnar
Dec 10, 2019·European Journal of Clinical Pharmacology·Sine DonnellanRobert J Walker

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