Volume 2 Supplement 1

18th International Symposium on Intensive Care and Emergency Medicine

Open Access

Pharmacokinetics of meropenem in intensive care patients receiving continuous renal replacement therapy

  • LJ Giles1,
  • AC Barber1,
  • G Creed1,
  • B Ng1,
  • RJ Beale1 and
  • A McLuckie1
Critical Care19982(Suppl 1):P130

DOI: 10.1186/cc259

Published: 1 March 1998

Introduction

This study was conducted to determine the appropriate dose of meropenem in critically ill patients with acute renal failure treated by continuous veno-venous haemofiltration (CVVH) or haemodiafiltration (CVVHDF) who require this antibiotic therapy.

Methods

Ten critically ill patients (7m, 3f, mean age 65 years (range: 51–77 years), mean weight 80 kg (range: 51–119 kg), mean APACHE II 27.7 (range: 21-37) were included. All patients were receiving CVVH (n = 5) (haemofiltration rate 1–2 l/h) or CVVHDF (n = 5) (haemofiltration rate 1–1.5 l/h: dialysis rate 1–1.5 l/h) using a polyacrylonitrile (AN69) hollow fibre 0.9 m2 filter (Multiflow 100, Hospal). All patients received a meropenem dose of 1 g 12 hourly, intravenously over 5 min. Venous serum samples were taken pre-dose and 5, 15, 30, 60, 90, 120, 240, 360, 480 min post-dose on day 3 to approximate steady state conditions. Haemofiltrate was collected for determination of a sieving coefficient. Samples were analysed by high performance liquid chromatography.

Results

Sieving coefficient for meropenem with the AN69 filter was 0.93 ± 0.06 (n = 9) indicating free flow across the membrane. Mean (± SD) serum concentrations at pre-dose, 5, 15, 30, 60, 90, 120, 240, 360, 480 mins post-dose were: 7.6 (5.1), 90.9 (23.9), 66.0 (13.0), 53.9 (15.7), 40.0 (10.3), 39.0 (9.2), 31.0 (10.4), 21.1 (6.9), 17.2 (6.2), 13.8 (6.4) mg/l respectively. Actual pre-dose (Ctrough), 5 min (Cpeak) and 480 min levels are given below. Serum concentrations remained above the MIC90 for Ps. aeruginosa (4 mg/l) in all patients for two-thirds of the dosage interval which is the target recommended for β-lactam antibiotics. A lower dose may not have been sufficient for all the patients.

Conclusion

A meropenem dose of 1 g 12 hourly is adequate in patients treated with CVVH or CVVHDF using an AN69 HF 0.9 m2 filter.

Table

Patient

1

2

3

4

5

6

7

8

9

10

Replacement

CVVH

    

CVVHDF

    

Rates (1/h)

1

1.5

2

2

2

1:1

1:1

1:1

1.5:1.5

1.5:1.5

Ctrough (mg/1)

13.3

4.2

3.4

7.2

14.6

13.3

2.5

6.3

0.5

10.8

Cpeak(mg/l)

90.1

127.7

85.2

73.2

81.7

116.3

101.2

115.0

63.1

55.3

C480mins (mg/l)

19.4

10.5

14.3

11.6

23.3

20.5

6.2

18.7

5.7

7.5

Authors’ Affiliations

(1)
Departments of Intensive Care and Pharmacy, Guy's Hospital

Copyright

© Current Science Ltd 1998

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