Effect Of Hematocrit On Pharmacokinetics Of Tacrolimus In Adult Living Donor Liver Transplant Recipients And Renal Transplant Recipients

ObjectiveLiver and kidney transplant patients who use Tacrolimus(FK506) as the main immunosuppressant as objects of study, this topic explores the impact of hematocrit fluctuations of transplant recipients who long-term use FK506 on the test results of the plasma concentration of FK506. And the differences of effects of hematocri of red blood cells on the test effects of hematocrit blood concentration of FK506 among liver and kidney transplant patients. The detached concentration of blood plasma is a direct efficacy of the concentration. The widely used immunoassay determination of enzyme amplification uses whole blood as a test sample. So this topic is to investigate the changes in the hematocrit on the import of detected results of whole blood drug concentration of FK506, to provide the reference for clinical detection of FK506, and to more accurately reflect the true concentration of FK506 in the patient serum. MethodsFirst, according to relevant vitro research of Tacrolimus pharmacokinetic, we analyze Tacrolimus human erythrocytes distribution’s vitro data. By using pharmacokinetic equation and according to the patient’s actual detection of FK506 whole blood drug concentration and patient’s hematocrit of red blood cells, we simulate to calculate the binding saturation of FK506 and red blood cells, and we also simulate to calculate the plasma concentration of FK506. To establish the experimental analysis methods of enzyme immunoassay amplification with high sensitivity, specificity and good accuracy to measure the blood concentration of FK506 in whole blood, and to inspect specificity, precision, accuracy of methods and quantitative detection range and linear, and to evaluate the detection methodology. The detection steps as following: Precisely draw six concentration standard solution, quality control product of various concentration, whole blood samples of 200 ul in 1.5ml centrifuge tubes(vibrating whole blood samples to be mixed in advance), and then added 200 ul precipitant(methanol) and pretreatment reagents of 50ul(copper sulfate), immediately and fully vortexed for 30 s, standing for 2min, 10800r/min centrifugal for 10 min. After centrifugation, all supernatant samples were poured out into tube on the machine to measure whole blood FK506 drug concentration. At the same time, precisely drawing tacrolimus control solution of different concentrations of low, medium and high, instrument can automatically fit quality control samples, and the result of concentration of the sample.Second, retrospectively analysis the drug dose of the liver transplantation recipient and the relationship between the drug concentrations of FK506 whole blood and the predicted drug of FK506 blood plasma;Third, retrospectively analysis the drug dose of the kidney transplantation recipient and the relationship between the drug concentrations of FK506 whole blood and the predicted drug of FK506 blood plasma. Results1. In the simulation study, FK506 plasma and the clearance of whole blood concentrations change with Hct, among the three meet certain function.2. The RSD fort intraday and interday assays of EMIT Level 1(low concentrations)、 Level 2(moderate concentrations)、Level 3(high concentrations) were 6.1%,3.5% 10.1%, 10.6%, 7.9%, 9.2% respectively; The recovery rate for the intraday and interday were 114%, 95.5%, 96.1%, 109.3%, 100.1%, 103.9% respectively. All of these conform to the regulations of biological sample testing RSD < 15% and method recovery rate between 85~115% of “Chinese Pharmacopoeia”. Measuring quality control materials Level 1(low), Level 2(middle), Level 3(high) up to 90 times, all within the control range, the test points in Level 1(low), Level 2(middle), Level 3(high) quality control figure falling within?x ± s are more than 69%. Level 1(low) and Level 3(high) quality control is better, but Level 2(middle) due to quality differences in quality control samples of different batches, quality control curves have slight fluctuations.3. FK506 drug concentrations in whole blood are kept within a certain therapeutic range for liver transplant recipients. However, the change of Hct presents diversity after patients’ liver transplantation. According to the research and findings, The correlation(R =-0.149, n = 302) of Hct and D / Cp(the ratio of FK506 dose and drug concentration in plasma) is lower than the correlation(R =-0.493, n = 302) of Hct and D / CWB(the ratio of FK506 dose and whole blood drug concentration).4. FK506 drug concentrations in whole blood are kept within a certain therapeutic range for kidney transplant recipients. However, the change of Hct presents diversity after patients’ kidney transplantation. According to research and the findings, the correlation(R =-0.556, n = 463) of Hct and D / Cp(the ratio of FK506 dose and drug concentration in plasma) is lower than the correlation(R =-0.778, n = 463) of Hct and D / CWB(the ratio of FK506 dose and blood concentration). ConclusionsThe EMIT method which measures the drug concentration of FK506 whole blood has good specificity and high precision. It is consistent with the clinical testing requirements of plasma concentration. The quality control standards established by laboratories are reliable and the experimental monitoring results are accurate.For long-term use of anti immune rejection FK506 drugs for liver or kidney transplant recipients, Hct is a very important influential factor of FK506 pharmacokinetics. Therefore, Hct should be taken into account in daily doses of FK506, especially when the Hematocrit is low. At the same time, it is especially important for liver transplant patients. It is recommended for liver transplant patients to monitor the drug FK506 of the plasma concentration that is more accurate to reflect the changes of blood concentration of liver transplant recipients.