Kidney Week

Abstract: SA-PO628

The Pharmacokinetics of Meropenem and Piperacillin/Tazobactam in Haemodiafiltration

Session Information

• Pharmacology
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Donnellan, Sine, Dunedin Hospital, Dunedin, New Zealand

Sine Donnellan,

• Wright, Dan, University of Otago, Dunedin, New Zealand

Dan Wright,

• Duffull, Stephen, University of Otago, Dunedin, New Zealand

Stephen Duffull,

• Putt, Tracey L., Dunedin Hospital, Dunedin, New Zealand

Tracey L. Putt,

• Schollum, John B.W., Dunedin Hospital, Dunedin, New Zealand

John B.W. Schollum,

• Walker, Robert J., University of Otago, Dunedin, New Zealand

Robert J. Walker,

Background

Meropenem and piperacillin/tazoobactam (PIPC/TAZ) are commonly used in the treatment of sepsis. Their effectiveness is dependent upon time above minimium inhibitory concentration (MIC). Dosing practices in haemodiafiltration (HDF) rely on extrapolation from intermittent haemodialysis (IHD) or continuous renal replacement therapies and may lead to subtherapeutic concentration due to fundamental differences in membrane characteristics, duration of therapy and blood flow rates.

Methods

We performed an open label pilot study on 6 stable haemodialysis patients. HDF prescription was based upon our local intensive care practice. Patient characteristics, bioimpendance and any deviation from prescription were documented. Meropenem (1g) was administered 1 hour prior to commencement of HDF. 12 blood samples were taken (baseline, pre, post membrane during HDF and 1 hour post cessation). This was repeated with PIPC/TAZ (4.5g) 1 week later. Samples were analysed by validated chromatography.Pharmacokinetic modelling analysis was performed on each of the samples using non-compartmental methods.Extrapolation of plasma concentrations to 12 hrs was approximated assuming an exponential decline, given by;
C_p(t) =C_p0 x e^-kt
were Cp(t) is the plasma concentration at time (12 hrs post=dose in this case),C_p0 is the plasma concentration at time 0, and k is the terminal phase rate constant.

Results

Participants were mostly male with a mean age of 63.8±14 yrs. Haemodiafiltration clearance (HDCL) ranged from 8.9-10.8 L/h for meropenem and 9.6-19.1 L/h for PIPC/TAZ with an area under the plasma concentration-time curve during HDF (AUC_HDF) of 83-99 and 195-351 mg/L*h respectively. Fig 1 shows approximation of the PIPC/TAZ and meropenem data assuming the HDF continued for 12 hours without repeated dosing.

Conclusion

Meropenem and PIPC/TAZ removal during HDF is substantial with potential subtherapeutic concentration after a relatively short period.