Related Experiment Video
Updated: Apr 21, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Are interstitial fluid concentrations of meropenem equivalent to plasma concentrations in critically ill patients
Julie M Varghese1, Paul Jarrett2, Steven C Wallis1
1Burns, Trauma & Critical Care Research Centre, The University of Queensland, Level 7, Block 6 Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia.
Objectives:
To describe the interstitial fluid (ISF) and plasma pharmacokinetics of meropenem in patients on continuous venovenous haemodiafiltration (CVVHDF).
Patients And Methods:
This was a prospective observational pharmacokinetic study. Meropenem (500 mg) was administered every 8 h. CVVHDF was targeted as a 2-3 L/h exchange using a polyacrylonitrile filter with a surface area of 1.05 m2 and a blood flow rate of 200 mL/min. Serial blood (pre- and post-filter), filtrate/dialysate and ISF concentrations were measured on 2 days of treatment (Profiles A and B). Subcutaneous tissue ISF concentrations were determined using microdialysis.
Results:
A total of 384 samples were collected. During Profile A, the comparative median (IQR) ISF and plasma peak concentrations were 13.6 (12.0-16.8) and 40.7 (36.6-45.6) mg/L and the trough concentrations were 2.6 (2.4-3.4) and 4.9 (3.5-5.0) mg/L, respectively. During Profile B, the ISF trough concentrations increased by ∼40%. Meropenem ISF penetration was estimated at 63% (60%-69%) and 69% (65%-74%) for Profiles A and B, respectively, using comparative plasma and ISF AUCs. For Profile A, the plasma elimination t1/2 was 3.7 (3.3-4.0) h, the volume of distribution was 0.35 (0.25-0.46) L/kg, the total clearance was 4.1 (4.1-4.8) L/h and the CVVHDF clearance was 2.9 (2.7-3.1) L/h.
Conclusions:
This is the first known report of concurrent plasma and ISF concentrations of a meropenem antibiotic during CVVHDF. We observed that the ISF concentrations of meropenem were significantly lower than the plasma concentrations, although the present dose was appropriate for infections caused by intermediately susceptible pathogens (MIC≤4 mg/L).
Insights
Meropenem concentrations in interstitial fluid (ISF) were lower than plasma during continuous venovenous haemodiafiltration (CVVHDF). However, the dose achieved adequate ISF levels for treating infections caused by susceptible pathogens.
Area of Science:
- Pharmacokinetics and drug disposition
- Critical care medicine
- Infectious diseases
Background:
- Continuous venovenous haemodiafiltration (CVVHDF) is common in critically ill patients.
- Understanding meropenem distribution in interstitial fluid (ISF) is crucial for effective treatment.
- Limited data exist on meropenem pharmacokinetics during CVVHDF.
Purpose of the Study:
- To determine meropenem concentrations in both plasma and ISF.
- To evaluate the pharmacokinetic profile of meropenem in patients undergoing CVVHDF.
- To assess meropenem penetration into ISF during CVVHDF.
Main Methods:
- Prospective observational pharmacokinetic study.
- Meropenem (500 mg) administered every 8 hours.
- ISF concentrations measured via microdialysis; plasma and filtrate concentrations also monitored.
Main Results:
- ISF meropenem concentrations were lower than plasma concentrations.
- Meropenem ISF penetration was estimated between 63-74%.
- Plasma elimination half-life was 3.7 hours; CVVHDF clearance was 2.9 L/h.
Conclusions:
- This study provides the first concurrent plasma and ISF meropenem concentrations during CVVHDF.
- Observed ISF concentrations suggest the standard dose is appropriate for susceptible pathogens.
- Further research may optimize dosing strategies in CVVHDF patients.
Related Concept Videos
01:30Continuous Renal Replacement Therapy
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
01:26Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
01:20Acute Kidney Injury V: Interprofessional Care
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...