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

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 clinical practice were explored. When AMC was dosed twice daily, the PTA was mostly ≥90% for both compounds regardless of when haemodialysis commenced. When administered once daily, the PTA was 20-30% for clavulanic acid and ≥90% for amoxicillin. The simulations suggest that once-daily orally administered AMC in patients receiving high-flux haemodialysis may result in insufficient concentrations of clavulanic acid to effectively treat infections, especially on days when haemodialysis occurs.

• Authors: Katrina Hui, Kashyap Patel, David C M Kong, Carl M J Kirkpatrick
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 50 Issue 1 Pg. 110-113 (Jul 2017) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 28502697 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• beta-Lactamase Inhibitors
• Amoxicillin-Potassium Clavulanate Combination

Topics

• Amoxicillin-Potassium Clavulanate Combination (administration & dosage, pharmacokinetics)
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Drug Therapy, Combination (methods)
• Humans
• Microbial Sensitivity Tests
• Monte Carlo Method
• Plasma (chemistry)
• Renal Dialysis (methods)
• Time Factors
• beta-Lactamase Inhibitors (administration & dosage, pharmacokinetics)