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AIM: To analyze the effect of influential factors on the estimation of pharmacokinetic parameters of teicoplanin, this study was proposed to develop the population pharmacokinetic (PPK) model of teicoplanin in patients with renal insufficiency. METHODS: A total of 66 routine blood teicoplanin concentration monitoring data were collected from 46 cases with renal insufficiency, and a nonlinear mixed effect modeling program was used to establish one-compartment model with Monolix 2021R1 software. Furthermore, 20 routine blood teicoplanin concentration monitoring data were also collected from the other 20 cases with renal insufficiency, and the external validation of the model was performed by goodness-of-fit parameter method. RESULTS: The one compartment model was an appropriate model for simulating the pharmacokinetics of teicoplanin in patients with renal insufficiency. The typical values of apparent volume of distribution and clearance rate were 148.9 L and 0.13 L/h, respectively. Glomerular filtration rate and body weight, instead of other factors, were the primary variables that affected the elimination of teicoplanin in vivo. CONCLUSION: The population pharmacokinetic model of teicoplanin established in the present study was effective and stable, which could also predict the dynamic change of teicoplanin concentration. As a result, the population pharmacokinetic model could provide references for the rational use of teicoplanin in special populations.
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Objective: To develop an HPLC method for the determination of ibrutinib in rat's plasma, and study its pharmacoki-netics. Methods: The analytical column was packed with ZORBAX XDB-C18(150 mm×4. 6 mm,5 μm). A mixture of acetonitrile-wa-ter-0. 1% trifluoroacetic acid (42 ∶ 31 ∶ 27) was used as the mobile phase with the flow rate at 1. 0 ml·min-1. The detection wave-length was set at 258 nm. The column temperature was set at 30℃. Carbamazepine was used as the internal standard. Plasma was ex-tracted under alkaline condition and ibrutinib was detected. Nine SD rats were treated with single dose of ibrutinib 15 mg·kg-1by in-tragastric administration. Blood samples were collected at different time points after ibrutinib administration. The plasma concentration of ibrutinib was detected, and the pharmacokinetic parameters were calculated by DAS software. Results: Excellent linear relationship was obtained within the range of 10 μg·L-1to 2 000 μg·L-1(r =0.999 7). The intra-day RSDs were 7.11%, 10.41% and 3. 19% , and the inter-day RSDs were 2. 56% , 1. 98% and 3. 79% respectively for three concentrations ( 25, 500 and 1 500 μg· L-1), the average recoveries were (78. 91 ± 2. 10)% , (86. 29 ± 3. 97)% and (83. 61 ± 2. 11)% , respectively. After intragastric administration of ibrutinib, the main pharmacokinetic parameters of ibrutinib were as follows:Cmaxwas(1 019.43 ±74.85)μg·L-1, Tmaxwas(4.78 ±1.20)h, AUC(0-36)was(10 417.26 ±2 167.51)μg·h·L-1, AUC(0-inf)was(10 956.72 ±2491.09)μg·h·L-1, and t1/2was(8.57 ±1.47)h. Conclusion: The method is simple, rapid and accurate, and can be applied in the studies on the phar-macokinetics of ibrutinib.
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Objective:To develop an HPLC method for the determination of nintedanib in rabbit plasma and study the pharmacoki-netics of nintedanib in rabbits. Methods:The separation was performed on an Agilent ZORBAX SB-C18 column. A mixture of acetoni-trile-0. 1% trifluoroacetic acid-water (35∶ 20∶ 45) was used as the mobile phase at a flow rate of 1. 0 ml·min-1. The detection wavelength was set at 286 nm. Carbamazepine was used as the internal standard and nintedanib was extracted by ethyl acetate from plasma under basic condition. Totally 6 rabbits were given 20 mg·kg-1 nintedanib with intravenous administration. The blood samples were collected from the auricular vein at different time points after the administration. The concentration of nintedanib in plasma was detected by the HPLC method. The pharmacokinetics parameters were analyzed by DAS program. Results: An excellent linear rela-tionship was obtained within the range of 0. 05-10. 00 μg·ml-1(r=0. 999 8). The intra-day RSD was 5. 55%, 4. 53% and 2. 74%and inter-day RSD was 6. 15%, 5. 45% and 3. 15%, respectively for the three concentrations(0. 10, 2. 50 and 7. 50μg·ml-1), and the relative recovery was (98. 50 ± 5. 47)%, (100. 25 ± 4. 54)% and (99. 94 ± 2. 74)%, respectively. The main pharmacokinetics parameters of nintedanib were as follows: Cmaxwas (3.01 ±0.35) μg·ml-1, t1/2 was (4.38 ±1.53) h and AUC0-t was (11.67 ± 1. 71) μg·h·ml-1 . Conclusion:The method is simple, rapid and accurate, and can be used to determine the nintedanib concentra-tion in rabbit plasma and study its pharmacokinetics. Nintedanib is fitted the first-order elimination kinetics in rabbits.
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A [cocktail] of several probe drugs is often used to evaluate metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among probe drugs can appear and may impact the rate of biotransformation of other ones. Our presented work was aimed on the influence of bupropion on cytochrome P450-mediated metabolism of tolbutamide. The biotransformation rates of tolbutamide administered either separately or in combined with bupropion were compared in this study. The results revealed that bupropion had no significant effect on tolbutamide hydroxylation. Thus, due to stability in cytochrome P450 enzyme metabolic activity in the case of combining of two model probe drugs the procedure can show to no extent differential results comparing to the single-marker use
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The nitric oxide donor drugs have the functions of anti-hyperplasia, inhibiting platelet adhesion and aggregation, regulating immune response, etc. It suggests that these drugs play important roles in therapy of cardiovascular diseases, male impotence and pregnancy-induced hypertension syndrome.