OBJECTIVE

2

To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency.

METHODS

2

The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied f

or Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT

＞4MIC

≥40% and

C

min

≤27.5 mg/L were calculated respectively to optimize the dosing regimen.

RESULTS

2

For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h” “1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h” “1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”，

C

min

＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur.

CONCLUSIONS

2

For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time.