Clinical Study On Cisplatin Clinical Pharmacokinetics And Early Renal Injury

Objective:1.Through analyzing20cases of malignant tumor patients with cisplatin (DDP) concentration in the body of blood,it is a preliminary study of DDP pharmacokinetic characteristics in the human body.2.To discuss the correlation of DDP blood concentration and DDP renal toxicity, especially relevant marker of early renal injury such as Microalbuminuria(M-Alb)、beta-2macroglobulin (B2-MG), for malignant tumor patients of renal toxicity in the process of cisplatin chemotherapy provide the early prevention, also offer a certain theoretical basis for individualized treatment of malignant tumor patients. Methods:1.Subjects:selecting20patients with malignant tumors, including10cases of lung cancer patients,6patients with cervical cancer, patients with parotid gland carcinoma, esophageal cancer, nasopharyngeal cancer, pancreatic cancer respectively Oncology department of affiliated hospital of Luzhou medical college between May2012and March2013were confirmed by histopathology and cytology.13cases of male, female7cases;41～55years old, average (45.2±4.9). Rule out other serious organic disease; Basic normal of liver and kidney function and blood in the urine and routine electrocardiogram; chemotherapy drugs is not taken before4weeks of this experiment.2.Blood samples:all the patients after DDP infusion0,30,60,120minutes,12,24and48hours take2ml of venous blood. Whole blood centrifuge for10min and3000r/min,absorbing the plasma layer. All specimens were saved-70℃in refrigerator to be detected by high performance liquid chemotherapy (HPLC)3.Analytical method validation and chromatographic column conditions:1.The analysis methods including precision, repeatability and recovery rate, etc.2. The chromatographic conditions:chromatographic column5UODS3100a Prodigy (250mm x4.6mm,5microns); mobile phase:water and methanol (5:1); the flow rate of1.0ml/min; detection wavelength of254nm; Column temperature:30℃.4.DDP blood drug concentration analysis method and determination:using method of high performance liquid chromatograph (HPLC) pre-column derivatization,namely with DDTC is complex; With NiCl2as internal standard substance was analyzed to DDP blood drug concentration.5. collecting Urine samples:chemotherapy with DDP before and after1,2,3days to collect the morning urine and place in refrigerator with-70℃, with Siemens ADVIA2400fully automatic biochemical instrument transmission immune turbid metric method in detecting level values of urine microalbuminuria (M-Alb),β2macroglobulin (β2-MG) Results:1. Plasma detection concentration in linear regression equation y=1.486+0.089x, r=0.9980; linear range:0.1～10ug/ml, the lowest detection limit (S/N>3)of plasma is50ng/ml; separate degree with DDP and NiCl2is greater than1.5, can finish the baseline separation; trailing factor with DDP and NiCl2is1.01and1.02respectively, the peak shape is good; Precision with between group and within a group of RSD<10%. Repeatability is good.; Accuracy rate was<15%; Freeze-thaw stability of RSD<15%; Cisplatin plasma concentrations measured maximum7.745μg/ml; A minimum of0.2154μg/ml.It accords with pharmacokinetic2chamber model change.2) pharmacokinetic analysis:cisplatin blood concentration of20cases of malignant tumor patients, by DAS2.0pharmacokinetic analysis software for data processing through different time points, establish cisplatin pharmacokinetic model and pharmacokinetic parameters in the human body, including:, area under Of blood drug concentration-time curve (AUC=26.607mg/ml·h), clearance (CL=2.721L/h/m2), apparent volume of distribution (Vd=14.985L/m2), the distribution of half-life ((t1/2α=0.953h)), elimination phase of half-life (t1/2β=13.338h), mean residence time(the MRT=5.967h), k10=0.182(1/h),k21=0.1209(1/h),k12=0.389(1/h)etc. It accords with pharmacokinetic2chamber model change. Analysis of statistical methods: through SPSS11.5software of DDP in vivo of blood concentration and urine microalbuminuria (M-Alb),β2macroglobulin (β2-MG) level for correlation analysis, take a=0.01as the inspection level, shows r=-0.622; r=+0.92respectively. DDP blood concentration in vivo and urine microalbuminuria (M-Alb) is negative correlation; with β2-microglobulin (β2-MG) level values is positively related. Conclusion:1.through this experiment with column derivatization method for DDP before the determination of blood drug concentration in the human body, for clinical pharmacokinetic study of DDP provides a practical, cheap, accurate detection method.2. the DDP in vivo blood drug concentration and DDP renal toxicity, that is, the indicators of early renal injury related to urine microalbuminuria (M-Alb) and β2-microglobuin,(β2-MG) have certain relevance. Hence this experiment for researching cisplatin chemotherapy in patients of malignant tumor provides research idea and preventive measures of possible renal toxicity, also provides DDP individualized treatment of malignant tumor patients with a certain theoretical basis.