Pharmacokinetics and pharmacodynamics of meropene administered by traditional prolonged infusion or optimized prolonged infusion in different tissues of septic rats

Abstract

Abstract:

AIM: To study the pharmacokinetics of meropenem infused through different methods in varied parts of septic rats by microdialysis and to evaluate the pharmacodynamics of the two different infusion methods using of Monte Carlo simulation. METHODS: Twelve male Sprague Dawley rats were randomly divided into two groups (traditional prolonged infusion vs. the optimized prolonged infusion, n=6) for the pharmacokinetics study. Microdialysis probes were inserted into the jugular vein, hind leg muscle, subcutaneous adipose tissue and lung. Pharmacokinetic parameters were calculated by non-compartmental analysis. Monte Carlo simulations(10 000 rats) were performed to calculate 40％fT>MIC and the probability of target attainment (PTA) at different MICs，then to compare the effect of two infusion models. RESULTS: The tissue distribution factors (AUCtissue(0 to 6 h)/AUCplasma(0 to 6 h) ratio) of the two groups were both less than 1 for lung, muscle and subcutaneous adipose tissue relative to plasma; the Tmaxs in plasma, lung, muscle and subcutaneous adipose tissue had statistically difference between the optimized prolonged infusion group and the traditional prolonged infusion method group; at different MICs, using the optimized prolonged infusion method, the PTA values of the 40%fT>MIC for the free meropenem in different tissues were higher than using the traditional prolonged infusion method. CONCLUSION: Using total plasma concentrations can overestimate the antibacterial activity of the drug and therefore its clinical efficacy. According to the pharmacokinetic of meropenem in the target infected tissues is more reasonable than plasma to guide the meropenem dosing regimen. Optimized prolonged infusion method is likely more reasonable than traditional prolonged infusion method.

Key words: sepsis, pharmacokinetics, pharmacodynamics, meropenem, Monte Carlo simulation

CLC Number:

R965.2

WU Yonglei, WANG Dan, ZHANG Suiyang, WANG Ying, SUN Qin. Pharmacokinetics and pharmacodynamics of meropene administered by traditional prolonged infusion or optimized prolonged infusion in different tissues of septic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(7): 767-774.

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