Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging f...Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion （6 h）. MTX concentrations were measured by using a reversed phase high-performance liquid chromatography （RP-HPLC） assay. Results： CSF MTX concentrations were （1.65±1.52）×10^-6, （4.3±3.34）× 10^-7, （1.46±1.10）×10^-7 and （3.19±4.38）×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation： Y=0.057 97＋0.010 82X （Y： CSF MTX concentration, X： Plasma MTX concentration, r=0.8357）. Conclusion： CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.展开更多
Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Thr...Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/mL, AUC (12 127.39±636.16)ng·h/mL and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.展开更多
The purpose of this study was to evaluate the pharmacokinetic parameters and bioavailability of the solid dispersion formulation of diclazuril after oral administration in rabbits in comparison with its known premix f...The purpose of this study was to evaluate the pharmacokinetic parameters and bioavailability of the solid dispersion formulation of diclazuril after oral administration in rabbits in comparison with its known premix form with feed additive.Plasma concentrations were determined by high-performance liquid chromatography（HPLC）.The areas under the plasma concentration curves（AUC0-∞） of diclazuril in solid dispersion and premix were 247.8±18.1μg/h/mL and 145.4±12.6μg/h/mL,respectively. The Cmax of diclazuril in solid dispersion and premix were 33.72±4.75 μg/mL and 10.42±3.4μg/mL, respectively, The t1/2 were 9.53±1.37 and 9.23±1.20 min, respectively. The oral bioavailability of drug solid dispersion was 1.7-fold higher than that of premix. From these data we concluded that diclazuril solid dispersion may be used as a potential anticoccidial preparation.展开更多
A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue d...A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetaminoiso-corydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In Oro, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetaminoisocorydine could not easily pass through the blood brain bather. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful infonnation for the in vivo pharmacology of 8-acetaminoisocorydine, and can he applied to new drug research. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of 'Medical Sciences. Production and hosting by Elsevier B.V.展开更多
Biapenem, a new parenteral carbapenem, has been widely used for treating bacterial infections. A simple, effective and accurate method based on solid-phase extraction （SPE） and HPLC was developed for the quantitativ...Biapenem, a new parenteral carbapenem, has been widely used for treating bacterial infections. A simple, effective and accurate method based on solid-phase extraction （SPE） and HPLC was developed for the quantitative determination of biapenem in human plasma. Stability and feasibility of the method was validated through a series of experiments. Using Vitamin B6 as an internal standard, analyte was separated on a Capcell Pak C18 column after SPE on Oasis hydrophilic-lipophilic balance （HLB） cartridge. The mobile phase was comprised of 0.05 mol/L NaH2PO4 （pH 5.7） and methanol （98：2, v/v） at a flow rate of 1.0 mL/min. Ultraviolet absorbance was measured at 300 nm. The calibration curve was linear in the concentration range of 0.04-50.00 μg/mL, and the lower limit of quantification was as low as 0.04 μg/mL. Recovery rates of biapenem at 0.10, 5.00, and 25.00 μg/mL were about 70%. The validated method has been successfully applied for quantifying biapenem in human samples and a pharmacokinetic study of 12 healthy volunteers who received three different doses （150, 300 and 600 mg） of biapenem by intravenous infusion. Our method has featured good accuracy and precision, and the processed sample was stable. Therefore, it can be propagated for clinical use.展开更多
文摘Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion （6 h）. MTX concentrations were measured by using a reversed phase high-performance liquid chromatography （RP-HPLC） assay. Results： CSF MTX concentrations were （1.65±1.52）×10^-6, （4.3±3.34）× 10^-7, （1.46±1.10）×10^-7 and （3.19±4.38）×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation： Y=0.057 97＋0.010 82X （Y： CSF MTX concentration, X： Plasma MTX concentration, r=0.8357）. Conclusion： CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.
基金This work was supported by grant from Science Investigation Fund of Ministry of Health of China(No96-1-250)
文摘Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/mL, AUC (12 127.39±636.16)ng·h/mL and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.
文摘The purpose of this study was to evaluate the pharmacokinetic parameters and bioavailability of the solid dispersion formulation of diclazuril after oral administration in rabbits in comparison with its known premix form with feed additive.Plasma concentrations were determined by high-performance liquid chromatography（HPLC）.The areas under the plasma concentration curves（AUC0-∞） of diclazuril in solid dispersion and premix were 247.8±18.1μg/h/mL and 145.4±12.6μg/h/mL,respectively. The Cmax of diclazuril in solid dispersion and premix were 33.72±4.75 μg/mL and 10.42±3.4μg/mL, respectively, The t1/2 were 9.53±1.37 and 9.23±1.20 min, respectively. The oral bioavailability of drug solid dispersion was 1.7-fold higher than that of premix. From these data we concluded that diclazuril solid dispersion may be used as a potential anticoccidial preparation.
基金supported by the "West Light Program (No.Y30447YXL1)""Build Coalitions of the National Academy of Sciences" of the Chinese Academy of Sciences (No.Y20475YLJ1)the Science and Technology Program of Gansu (No.1304FKCA062)
文摘A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetaminoiso-corydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In Oro, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetaminoisocorydine could not easily pass through the blood brain bather. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful infonnation for the in vivo pharmacology of 8-acetaminoisocorydine, and can he applied to new drug research. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of 'Medical Sciences. Production and hosting by Elsevier B.V.
基金National Natural Science Foundation of China (Grant No.30973597)
文摘Biapenem, a new parenteral carbapenem, has been widely used for treating bacterial infections. A simple, effective and accurate method based on solid-phase extraction （SPE） and HPLC was developed for the quantitative determination of biapenem in human plasma. Stability and feasibility of the method was validated through a series of experiments. Using Vitamin B6 as an internal standard, analyte was separated on a Capcell Pak C18 column after SPE on Oasis hydrophilic-lipophilic balance （HLB） cartridge. The mobile phase was comprised of 0.05 mol/L NaH2PO4 （pH 5.7） and methanol （98：2, v/v） at a flow rate of 1.0 mL/min. Ultraviolet absorbance was measured at 300 nm. The calibration curve was linear in the concentration range of 0.04-50.00 μg/mL, and the lower limit of quantification was as low as 0.04 μg/mL. Recovery rates of biapenem at 0.10, 5.00, and 25.00 μg/mL were about 70%. The validated method has been successfully applied for quantifying biapenem in human samples and a pharmacokinetic study of 12 healthy volunteers who received three different doses （150, 300 and 600 mg） of biapenem by intravenous infusion. Our method has featured good accuracy and precision, and the processed sample was stable. Therefore, it can be propagated for clinical use.
