Use of SAS iteration and Monte Carlo simulation to optimize use of Meropenem

Abstract

Abstract: AIM: To choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms, meanwhile to evaluate pharmacodynamics of traditional(TIT),prolonged(PIT) and optimized two-step infusion therapy(OTIT) of Meropenem.METHODS: Firstly, use ofSAS iteration to choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms in the condition of two-step infusion therapy;secondly,use of Monte Carlo Simulation to calculate the %T>MIC and the probability of target attainments(PTAs) of TIT,PIT and OTIT, respectively.RESULTS:Based on the MICs of 1,2,4 μg/mL and means of CL and V_d, the dosing regimens of OTIT with 500 mg, 0.25 h/100 mg+2.75 h/400 mg; 500 mg, 0.25 h/250 mg+2.75 h/250 mg and 1000 mg, 0.25 h/400 mg+2.75 h/600 mg provided the highest %T>MIC with SAS iteration, respectively. Monte Carlo Simulation revealed that PIT and OTIT obtained higher %T>MIC and PTAs compared with TIT at different MICs,Meanwhile OTIT obtained shorter the time to maximum concentration(t_max) compared with PIT.CONCLUSION: SAS iteration may be performed to choose the best optimized dosages and regimens of antibiotics. Monte Carlo simulation may be performed to compare pharmacodynamic parameters of different dosing regimens.These results suggested that OTIT was better therapy against clinically serious infections.

Key words: Iteration, Monte Carlo simulation, Meropenem, Optimized Two-step infusion therapy

CLC Number:

R978.1

SHEN Hui-feng, ZHANG Sui-yang, CHANG Yan, REN Juan. Use of SAS iteration and Monte Carlo simulation to optimize use of Meropenem[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(5): 529-535.

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