| Object A simple, precise and rapid high perfomance liquid chromatographic method has been developed for the determination of meropenem in human serum. This method was used to measure meropenem's plasma concentration of patient with CVVH. By comparing meropenem's PK/PD parameter of traditional 30 minutes infusion,3 hours infusion and continuous infusion, we choose the best treatment protocols.Method Using High perfomanceliquid chromatograiphy for the measurement of concentration of Meropenem in serum. We use Venusil MP C18 chromatographic column(250mmx4.6mm; 5μm), the mobile phase consisted of 10.53mmol·L-1 ammonium acetate-acetonitrile (90:05, v/v) (pH 4) with glacial acetic acid, the velocity of flow being 1.0ml-min-1, The UV detection was at 298 nm.Drawing the standard curve, determinating the recovery rate and the degree of precison, detecting the plasma concentration of CVVH patients which were treated respectively by three different infusion way of Meropenem.27 patients were treated by CVVH and by Meropenem to anti-infection therapy. They were divided into A, B, C groups randomly.Meropenem were given to patients by three different infusion way. A group (n=9):30-minutes infusion,0.5g, pumping into vein during 30min, q8h; B group (n=9):3-h infusion,pumping into vein during 3h, q8h; C group (n=9):continuous infusion after pumping 0.25g loading dose into vein uniformly during 10min, we pumped 1.5g loading dose into vein uniformly during 24h. We drawed 2ml blood from central vein of extracorporal circulation at different time point after dosing (0.25h,0.5h,0.75, 1h,1.5h,2h,2.5h,3h,4h,5h,6h,7h and 8h). Then we put these blood samples into serum tube, centrifuged at 3000 r·min-1, seperated serum and stored in -70℃. The plasma concentration of Meropenem would be determinated by High perfomance liquid chromatograiphy. After established drug-time curve, we would compare the effection to Meropenems'PK/PD parameter (%T>MIC) of CVVH patients by three infusion way and survey if there were statistically differences among these different infusion way. The determination of the drug resistance (R), intermediate sueceptible (I) and susceptible (S) of Meropenem were all calculated according to stated breakpoints from papers of M100-S19 in Clinical and Laboratory Standards Institute (CLSI) at 2009.Results The standard curve equation of Meropenem's plasma concentration was C=0.35747A+0.06445, r=0.999996. The linearity range was 0.1-200μg·mL-1. The recovery was 96.704%-101.493%(n=6); the relative standard deviation(C.V) of intraday was 2.44%-4.855%(n=6) and it of interday was 2.444%-5.740%(n=3).Following 30-min infusion of 0.5g meropenem, the percentages of the T> MIC of 16,8,4 and 1μg·mL-1 were 13.28±7.30%,31.56±12.33%,51.00±11.77% and 96.69±7.90%, respectively. For the 3-h infusion of 0.5 g meropenem, the percentages of the t>MIC of 16,8,4 and 1μg·mL-1 were 1.98±5.94%,57.50±22.62%,89.97±11.50% and 100%. For continuous infusion way, the percentages of the t>MIC of 16,8,4 and 1μg·mL-1 were 15.81±30.70%,77.63±44.01%,100% and 100%. Three infusion way all had no any side effects related to Meropenem.Conclusion This method which was used for the determination of Meropenem's plasma concentration is sensitive, exact, rapid, simple and had high specificity and ruggedness. It can be used for the determination of Meropenem's plasma concentration and its study of PK/PD.For those patients with acute renal insufficiency and treated by CVVH, prolonging the time of IV Meropenem can improve the percentages of the T>MIC of many kinds of pathogenic bacteria's therapy. When the pathogenic bacteria's MIC≤4μg·mL-1,0.5g q8h of 30-min infusion,3-h infusion and continuous infusion have the same safety and validity; when the pathogenic bacteria's MIC was 8μg·mL-1, we advised 0.5g q8h of 3-h infusion and continuous infusion; when the pathogenic bacteria's MIC≥16μg·mL-1, we recommended add the dosage or change other sensitive test for Meropenem is resistant, we recommend adding dosage or replacing other antimicrobial agents. |
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