ABSTRACT
OBJECTIVE: To monitor and investigate the influencing factors of 6-methylmercaptopurine ribonucleotides (6-MMPR) in human red blood cell (RBC) in Chinese kidney transplant recipients treated with azathiopurine (AZA), and to provide references for clinical personalized medicine. METHODS: In 100 Chinese kidney transplant recipients, the concentration of 6-MMPR in RBC was detected by validated HPLC-UV method. Correlation analysis was performed to analyze the effects of various factors, including patient age, gender, weight, AZA dose and thiopurine S-methyltransferase (TPMT) activity, on the 6-MMPR concentration, and multivariate linear regression analysis was performed using SPSS20.0 software to investigate the influencing factors of 6-MMPR concentration. RESULTS: The concentration of 6-MMPR in 100 Chinese kidney transplant recipients was not normally distributed (P0.05), however, there was a significant positive correlation between TPMT activity and 6-MMPR concentration in RBC (P<0.001). CONCLUSION: TPMT activity in RBC is an independent factor affecting 6-MMPR concentration, which in turn affects the clinical efficacy and toxicity of the drug.
ABSTRACT
To observe the pharmacokinetic and tissue-distribution characters of 5-flourouracil magnetic albumin deuto-microsphere (5-Fu-MAD) in normal and tumor-bearing mice, HPLC method for the determination of 5-Fu in plasma and tissues was established and applied to determine 5-Fu in mouse plasma and tissue samples. A Flame atomic absorption spectrometer was used to detect the iron concentration in mouse tissue. Plasma concentration-time curves of free 5-Fu, 5-Fu-MAD and 5-Fu-MAD plus the magnetic frame (MF) conformed to two compartment model of first order absorption and they had C(max) of 34.9, 7.95 and 5.97 mg x L(-1); T1/2 (Ke) of 22.26, 76.0 and 124.6 min, V(d) of 3.28, 30.7 and 66.1 L x kg; AUC(0-t), of 233.9, 78.3 and 50.2 mg x min x L(-1); AUC(0-infinity) of 237.2, 89.3 and 68.1 mg x min x L(-1), respectively. The distribution of 5-Fu and iron was the highest in the plenty blood perfusion organs like the liver, tumor, spleen and lung, while lower in the kidney and heart and lowest in brain and muscle. The tissue distribution of muscle and tumor increased significantly when a magnetic frame was inserted there. The pharmacokinetics and tissue distribution of 5-Fu-MAD exhibited sustained-release and target characteristics.
Subject(s)
Animals , Female , Male , Mice , Albumins , Chemistry , Antimetabolites, Antineoplastic , Pharmacokinetics , Area Under Curve , Cell Line, Tumor , Delayed-Action Preparations , Fluorouracil , Pharmacokinetics , Liver , Metabolism , Pathology , Liver Neoplasms, Experimental , Metabolism , Pathology , Magnetics , Microspheres , Random Allocation , Tissue DistributionABSTRACT
<p><b>AIM</b>To establish an HPLC method for the determination of daurisoline (DS) in rabbit plasma and investigate its pharmacokinetic characteristics after intravenous administration.</p><p><b>METHODS</b>Dauricine was used as internal standard. The plasma samples were deproteinated with acetonitrile and extracted with two-step dichloromethane. Acetonitrile-water-triethylamine (18:82:0.28, pH 3) was used as mobile phase at a flow rate of 1.0 mL.min-1. The UV-detector was set at 284 nm.</p><p><b>RESULTS</b>The linear range was 0.05-20.00 micrograms.h.mL-1 with correlation coefficients 0.9996. The limit of quantitation (LOQ) was 0.05 mg.L-1 of plasma. The absolute and relative recoveries were above 80% and (101 +/- 5)%, respectively. The intra- and inter-assay coefficient of variation were 1.9%-5.6% and 3.5%-6.5%, respectively. The plasma concentration-time profiles were adequately described by a two-compartment open model.</p><p><b>CONCLUSION</b>A sensitive, precise and accurate method for the determination of DS in plasma was described, which can be used in its pharmacokinetic studies.</p>