The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Leslie Z. Benet - One of the best experts on this subject based on the ideXlab platform.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous ciprofloxacin and rifampin, multiple doses of rifampin, on glyburide exposure and effect on blood glucose levels in 9 healthy volunteers were investigated. The single intravenous dose of rifampin significantly increased the AUCs of glyburide and Metabolite. Blood glucose levels dropped significantly in comparison to when glyburide was dosed alone. Multiple doses of rifampin induced liver enzymes leading to a marked decrease in glyburide exposure and in blood glucose measurements. When intravenous rifampin was given after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect, however, relative changes in AUC for glyburide and its hydroxyl Metabolite were the same as that seen under non-induced conditions. The studies reported here demonstrate how measurements of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and characterizing enzymatic versus transporter mechanisms.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its Metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl Metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.
Li Ding - One of the best experts on this subject based on the ideXlab platform.
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Development and validation of samples stabilization strategy and LC-MS/MS method for simultaneous determination of clevidipine and its Primary Metabolite in human plasma: Application to clinical pharmacokinetic study in Chinese healthy volunteers.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2020Co-Authors: Yujia Zhang, Shunbo Zhao, Huan Zhou, Li DingAbstract:Abstract A feasible LC-MS/MS method with reliable stabilizers consisted of sodium fluoride, ascorbic acid and formic acid was developed and validated for the determination of clevidipine and its Primary Metabolite (H152/81) in human plasma. Sodium fluoride existing in the vacutainer tubes was used to inhibit esterase activity to protect the clevidipine from hydrolysis as soon as blood was collected. Ascorbic acid and formic acid were added to the separated plasma samples to avoid the oxidation and further hydrolysis of clevidipine and H152/81. The further sample preparation was accomplished through a single step liquid-liquid extraction (LLE) by ethyl acetate. The chromatography separation was carried out on an ACE Excel 3 μm SuperC18 (2.1 × 50 mm, id, ACE, United Kingdom) column with gradient elution using 10 mM ammonium acetate water solution and methanol as the mobile phase. Detection was performed in the negative ion electrospray ionization mode using multiple reaction monitoring (clevidipine: m/z 454.1 → 234.0; clevidipine-d7: m/z 461.1 → 240.1; H152/81: m/z 354.0 → 208.0; H152/81-13CD3: m/z 358.0 → 212.0). The method exhibited good linearity over the concentration ranges of 0.100 to 40.0 ng/mL for clevidipine and 5.00 to 400 ng/mL for H152/81. The intra- and inter-batch precision and accuracy of clevidipine and H152/81 were all within the acceptable criteria. The method was successfully applied to a pharmacokinetic study of clevidipine and H152/81 in healthy Chinese volunteers following 8 mg/h intravenous infusion of clevidipine butyrate injectable emulsion for 0.5 h. The results showed that clevidipine was rapidly eliminated with a short half-life time of 0.244 ± 0.125 h and a maximum concentration of 25.2 ± 7.09 ng/mL. H152/81 was detectable in the plasma samples up to 48.5 h with a half-life time of 10.7 ± 2.30 h and a maximum plasma concentration of 301 ± 38.1 ng/mL.
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pharmacokinetics and tissue distribution study of clevidipine and its Primary Metabolite h152 81 in rats
Biomedical Chromatography, 2018Co-Authors: Lanting Zhao, Yan Wang, Wen Yang, Lu-ning Sun, Li DingAbstract:This present study was designed to investigate the pharmacokinetic profiles and tissue distribution characteristics of clevidipine and its Primary Metabolite H152/81 in rats following a single intravenous administration of clevidipine butyrate injectable emulsion. For this study, a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated for the simultaneous quantitation of clevidipine and H152/81 in rat whole blood and various tissues. A Hedera ODS-2 column with two gradient elution programs was employed for the troubleshooting of matrix effect on the detection of analytes among different biological samples. The experimental data showed that clevidipine represented quick elimination from blood with a half-life of about 4.3 min and rapid distribution in all of the investigated tissues after administration; the highest concentration of clevidipine was found in the heart whereas the lowest concentration was detected in the liver. In addition, clevidipine was almost undetectable in most tissues except for heart and brain at 90 min post-dosing, suggesting that there was no apparent long-term accumulation in rat tissues. For H152/81, the peak concentration of 3714 ± 319 ng/mL occurred at 0.129 ± 0.048 h, the half-life was 10.08 ± 1.45 h and area under the concentration-time curve was 42091 ± 3812 ng h/mL after drug administration. In addition, H152/81 was found at significant concentration levels in all tissues, in descending order of lung, kidney, heart, liver, spleen and brain at each time point. The results of current study offer useful clues for better understanding the distribution and metabolism of clevidipine butyrate injectable emulsion in vivo.
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Pharmacokinetics and tissue distribution study of clevidipine and its Primary Metabolite H152/81 in rats.
Biomedical chromatography : BMC, 2017Co-Authors: Yan Wang, Lanting Zhao, Wen Yang, Lu-ning Sun, Li DingAbstract:This present study was designed to investigate the pharmacokinetic profiles and tissue distribution characteristics of clevidipine and its Primary Metabolite H152/81 in rats following a single intravenous administration of clevidipine butyrate injectable emulsion. For this study, a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated for the simultaneous quantitation of clevidipine and H152/81 in rat whole blood and various tissues. A Hedera ODS-2 column with two gradient elution programs was employed for the troubleshooting of matrix effect on the detection of analytes among different biological samples. The experimental data showed that clevidipine represented quick elimination from blood with a half-life of about 4.3 min and rapid distribution in all of the investigated tissues after administration; the highest concentration of clevidipine was found in the heart whereas the lowest concentration was detected in the liver. In addition, clevidipine was almost undetectable in most tissues except for heart and brain at 90 min post-dosing, suggesting that there was no apparent long-term accumulation in rat tissues. For H152/81, the peak concentration of 3714 ± 319 ng/mL occurred at 0.129 ± 0.048 h, the half-life was 10.08 ± 1.45 h and area under the concentration-time curve was 42091 ± 3812 ng h/mL after drug administration. In addition, H152/81 was found at significant concentration levels in all tissues, in descending order of lung, kidney, heart, liver, spleen and brain at each time point. The results of current study offer useful clues for better understanding the distribution and metabolism of clevidipine butyrate injectable emulsion in vivo.
H X Zheng - One of the best experts on this subject based on the ideXlab platform.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous ciprofloxacin and rifampin, multiple doses of rifampin, on glyburide exposure and effect on blood glucose levels in 9 healthy volunteers were investigated. The single intravenous dose of rifampin significantly increased the AUCs of glyburide and Metabolite. Blood glucose levels dropped significantly in comparison to when glyburide was dosed alone. Multiple doses of rifampin induced liver enzymes leading to a marked decrease in glyburide exposure and in blood glucose measurements. When intravenous rifampin was given after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect, however, relative changes in AUC for glyburide and its hydroxyl Metabolite were the same as that seen under non-induced conditions. The studies reported here demonstrate how measurements of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and characterizing enzymatic versus transporter mechanisms.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its Metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl Metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.
Lynda A Frassetto - One of the best experts on this subject based on the ideXlab platform.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous ciprofloxacin and rifampin, multiple doses of rifampin, on glyburide exposure and effect on blood glucose levels in 9 healthy volunteers were investigated. The single intravenous dose of rifampin significantly increased the AUCs of glyburide and Metabolite. Blood glucose levels dropped significantly in comparison to when glyburide was dosed alone. Multiple doses of rifampin induced liver enzymes leading to a marked decrease in glyburide exposure and in blood glucose measurements. When intravenous rifampin was given after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect, however, relative changes in AUC for glyburide and its hydroxyl Metabolite were the same as that seen under non-induced conditions. The studies reported here demonstrate how measurements of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and characterizing enzymatic versus transporter mechanisms.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its Metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl Metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.
Yong Huang - One of the best experts on this subject based on the ideXlab platform.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous ciprofloxacin and rifampin, multiple doses of rifampin, on glyburide exposure and effect on blood glucose levels in 9 healthy volunteers were investigated. The single intravenous dose of rifampin significantly increased the AUCs of glyburide and Metabolite. Blood glucose levels dropped significantly in comparison to when glyburide was dosed alone. Multiple doses of rifampin induced liver enzymes leading to a marked decrease in glyburide exposure and in blood glucose measurements. When intravenous rifampin was given after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect, however, relative changes in AUC for glyburide and its hydroxyl Metabolite were the same as that seen under non-induced conditions. The studies reported here demonstrate how measurements of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and characterizing enzymatic versus transporter mechanisms.
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elucidating rifampin s inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its Primary Metabolite
Clinical Pharmacology & Therapeutics, 2009Co-Authors: H X Zheng, Lynda A Frassetto, Yong Huang, Leslie Z. BenetAbstract:The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its Metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl Metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its Primary Metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.
