An Experimental Study On Pharmacokinetics Of Early Administration Of Imipenem And Its Effects On Inflammatory Cytokines After Severe Burns

ObjectiveTo study the change of pharmacokinetic parameters of early administrationof Imipenem and its effects on inflammatory cytokines in the interstitial fluidsunder eschar and plasma in the early stage after severe burns. Thus referencetheory foundation about early administration of broad-spectrum antibiotic in theshort stage after severe burns in the early stage could be offered.Methods1. An experiment study on changes of pharmacokinetic parameters of early administration of rniipenem in the interstitial fluids under eschar and plasma in the early stage after severe burns16 rabbits were separated into 2 groups by completely random design,A group (n=8):burn group;B group (n=8):control group. Early administration lOOmg of Imipenem in vein in the early stage after severe burns in 20 minutes in two groups,Exponents of the plasma and interstitial fluids under eschar were collected on the selected tune points. Concentrations of Imipenem in the interstitial fluids and plasma were determined by high performance liquid chromatography and microbial agar diffusion method. Pharmacokinetic parameters of Imipenem were produced by program 3p87.2. An experiment study on effects to inflammatory cytokines with early administration of Imipenem after severe burns16 rabbits were separated into 2 groups by completely random design,T group (n=8):experimental group,administration lOOmg of Imipenem in vein,Tid x 3 days;C group (n=8):control group,without administration of Imipenem. Exponents of the interstitial fluids under eschar and plasma were collected on the selected time points and determined by ELASA. Experimental data were statistically analyzed by program package SPSS 8.0.Results1. Compared to those in B group,pharmacokinetic parameters of Imipenem exhibited evident difference,half-life (TAP) prolonged,(1.53 + 0.27)h in plasma and (2.53 +0.42)h in the interstitial fluids of A group,(1.04+0.16)h hi plasma of B group;Elimination constant (P ) shortened,(0.47+0.07)l/h in plasma and (0.28 + 0.05) 1/h in the interstitial fluids under eschar of A group,(0.68+0.10)l/h in plasma of B group;Aera under curve (AUC) prolonged,(22. 68 + 7. 64) ug h m"1 in plasma of A group and (15.15+2. 96) ug hnf1 in plasma of B group;Plasma clearance (Cls) shortened,(4.91 + 1.43) L/h in plasma of A group and (6. 81 +1. 17) L/h in plasma of B group. There were statistically significant at chosen level a =0.05 in two groups of the results of levels of TKB,P,AUC and Cls. Imipenem could be detected in the interstitial fluids of burn rabbits in Ih after the first initial dose of 100mg. 2 . Levels of IL-6,IL-8 and TNF-a in plasma increased in two groups after burned,Compared to C group,levels of IL-6,IL-8 and TNF-a in the interstitial fluids under eschar and plasma decreased evidently in T group. There were statistically significant at chosen level a =0.05 in two groups of the results of levels of IL-6,IL-8 and TNF-a.ConclusionHalf time of Imipenem prolonged evidently in the interstitial fluids under eschar and plasma in burn rabbits than in normal rabbits. The antibiotic barrier could be formed in the interstitial fluids with early administration of Imipenem in the early stage of burn,prevent an invasive bacterial infection from burn wound. Levels of IL-6,IL-8 and TNF-a hi interstitial fluids under eschar and plasma decreased evidently with early administration of Imipenem. It could help to relieve inflammationresponse of total body in burn patients. It achieved to postpone SIRS,Sepsis and MODS. It offered the reference theory that early and short-term use of antibiotics with broad-spectrum in severe burned patients could effectively prevent postburn severe infection.