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Michael J Avram - One of the best experts on this subject based on the ideXlab platform.
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drug induced hemodynamic perturbations alter the disposition of markers of blood volume extracellular fluid and total body water
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: Tom C Krejcie, Zhao Wang, Michael J AvramAbstract:Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and Antipyrine facilitate description of intravascular mixing and tissue distribution following intravenous administration. These models characterized physiologic marker disposition in four awake dogs under control conditions and during phenylephrine, isoproterenol, and nitroprusside infusions. Systemic vascular resistance was more than doubled by phenylephrine and was decreased more than 50% by both isoproterenol and nitroprusside. Dye (ICG) dilution cardiac output (CO) was decreased nearly one-third by phenylephrine, was more than doubled by isoproterenol, and was largely unaffected by nitroprusside. Although phenylephrine reduced CO, the fraction of CO represented by nondistributive blood flow nearly doubled at the expense of blood flow to rapidly equilibrating tissues. The area under the blood Antipyrine concentration versus time relationship for 3 min after administration (AUC(0-3 min)) during the phenylephrine infusion was nearly 75% larger than control due to both increased first-pass AUC and an increased fraction of CO represented by nondistributive blood flow. The large increase in CO produced by isoproterenol increased blood flow to rapidly equilibrating tissues and relatively decreased blood flow to slowly equilibrating tissues, because some appeared to equilibrate rapidly. Antipyrine AUC(0-3 min) during the isoproterenol infusion decreased more than 30%, due to decreased first-pass AUC. Nitroprusside changed Antipyrine intercompartmental clearances in proportion to CO and, hence, had little effect on Antipyrine AUC(0-3 min). These data provide further evidence that changes in Antipyrine (a lipophilic drug surrogate) blood flow-dependent distribution after rapid i.v. administration are not proportional to changes in CO but depend on both CO and its distribution.
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modifications of blood volume alter the disposition of markers of blood volume extracellular fluid and total body water
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Tom C Krejcie, Thomas K Henthorn, Claus U Niemann, W B Gentry, C A Shanks, C Endersklein, Michael J AvramAbstract:Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and Antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither Antipyrine-defined total body water volume nor Antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the Antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the Antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) Antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO.
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recirculatory pharmacokinetic models of markers of blood extracellular fluid and total body water administered concomitantly
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: Tom C Krejcie, Thomas K Henthorn, Claus U Niemann, C Klein, Dhanesh K Gupta, W B Gentry, C A Shanks, Michael J AvramAbstract:Pharmacokinetic models were developed to describe the disposition of markers of extracellular fluid (inulin) and total body water (Antipyrine) from the moment of injection to incorporate the intravascular mixing component, determined by a marker of intravascular space (indocyanine green, ICG). The simultaneous dispositions of these markers were characterized in four halothane-anesthetized dogs. After injection of ICG, [14C]-inulin, and Antipyrine into the right atrium, femoral arterial blood samples were collected every 3 sec for 1 min and less frequently to 20 min for ICG and to 360 min for inulin and Antipyrine. ICG and Antipyrine concentrations were measured by high-performance liquid chromatography and [14C]-inulin concentrations were measured by liquid scintillation counting. The marker concentration histories were characterized completely by fully identifiable recirculatory compartmental models. Because neither ICG nor inulin distribute beyond intravascular space before recirculation, their first-pass data were modelled simultaneously to improve confidence in central circulation model parameters. This central circulation model included an estimate of cardiac output that was retained in the recirculatory models of all markers. Three tissue compartments were identified for Antipyrine, a lipid soluble marker that equilibrates with tissue (including the lung) and estimates total body water and tissue blood flow. The hydrophilic marker, inulin, diffuses into interstitial fluid so slowly that only two extravascular compartments were identified. These models may be used to determine how cardiac output and its distribution, pulmonary drug uptake, and nondistributive blood flow contribute to variability in patient response to drugs with a rapid onset of effect.
Tom C Krejcie - One of the best experts on this subject based on the ideXlab platform.
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drug induced hemodynamic perturbations alter the disposition of markers of blood volume extracellular fluid and total body water
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: Tom C Krejcie, Zhao Wang, Michael J AvramAbstract:Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and Antipyrine facilitate description of intravascular mixing and tissue distribution following intravenous administration. These models characterized physiologic marker disposition in four awake dogs under control conditions and during phenylephrine, isoproterenol, and nitroprusside infusions. Systemic vascular resistance was more than doubled by phenylephrine and was decreased more than 50% by both isoproterenol and nitroprusside. Dye (ICG) dilution cardiac output (CO) was decreased nearly one-third by phenylephrine, was more than doubled by isoproterenol, and was largely unaffected by nitroprusside. Although phenylephrine reduced CO, the fraction of CO represented by nondistributive blood flow nearly doubled at the expense of blood flow to rapidly equilibrating tissues. The area under the blood Antipyrine concentration versus time relationship for 3 min after administration (AUC(0-3 min)) during the phenylephrine infusion was nearly 75% larger than control due to both increased first-pass AUC and an increased fraction of CO represented by nondistributive blood flow. The large increase in CO produced by isoproterenol increased blood flow to rapidly equilibrating tissues and relatively decreased blood flow to slowly equilibrating tissues, because some appeared to equilibrate rapidly. Antipyrine AUC(0-3 min) during the isoproterenol infusion decreased more than 30%, due to decreased first-pass AUC. Nitroprusside changed Antipyrine intercompartmental clearances in proportion to CO and, hence, had little effect on Antipyrine AUC(0-3 min). These data provide further evidence that changes in Antipyrine (a lipophilic drug surrogate) blood flow-dependent distribution after rapid i.v. administration are not proportional to changes in CO but depend on both CO and its distribution.
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modifications of blood volume alter the disposition of markers of blood volume extracellular fluid and total body water
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Tom C Krejcie, Thomas K Henthorn, Claus U Niemann, W B Gentry, C A Shanks, C Endersklein, Michael J AvramAbstract:Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and Antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither Antipyrine-defined total body water volume nor Antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the Antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the Antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) Antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO.
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recirculatory pharmacokinetic models of markers of blood extracellular fluid and total body water administered concomitantly
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: Tom C Krejcie, Thomas K Henthorn, Claus U Niemann, C Klein, Dhanesh K Gupta, W B Gentry, C A Shanks, Michael J AvramAbstract:Pharmacokinetic models were developed to describe the disposition of markers of extracellular fluid (inulin) and total body water (Antipyrine) from the moment of injection to incorporate the intravascular mixing component, determined by a marker of intravascular space (indocyanine green, ICG). The simultaneous dispositions of these markers were characterized in four halothane-anesthetized dogs. After injection of ICG, [14C]-inulin, and Antipyrine into the right atrium, femoral arterial blood samples were collected every 3 sec for 1 min and less frequently to 20 min for ICG and to 360 min for inulin and Antipyrine. ICG and Antipyrine concentrations were measured by high-performance liquid chromatography and [14C]-inulin concentrations were measured by liquid scintillation counting. The marker concentration histories were characterized completely by fully identifiable recirculatory compartmental models. Because neither ICG nor inulin distribute beyond intravascular space before recirculation, their first-pass data were modelled simultaneously to improve confidence in central circulation model parameters. This central circulation model included an estimate of cardiac output that was retained in the recirculatory models of all markers. Three tissue compartments were identified for Antipyrine, a lipid soluble marker that equilibrates with tissue (including the lung) and estimates total body water and tissue blood flow. The hydrophilic marker, inulin, diffuses into interstitial fluid so slowly that only two extravascular compartments were identified. These models may be used to determine how cardiac output and its distribution, pulmonary drug uptake, and nondistributive blood flow contribute to variability in patient response to drugs with a rapid onset of effect.
Andrea Melchior - One of the best experts on this subject based on the ideXlab platform.
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differential metal ion sensing by an Antipyrine derivative in aqueous and β cyclodextrin media selectivity tuning by β cyclodextrin
Analytical Chemistry, 2018Co-Authors: Govindaraj Tamil Selvan, Sumathi Poomalai, Sivaraj Ramasamy, Paulraj Mosae Selvakumar, Israel V M V Enoch, Sara Gracia Lanas, Andrea MelchiorAbstract:β-Cyclodextrin (β-CD) is a nontoxic cyclic oligosachcharide that can encapsulate all or part of organic molecules of appropriate size and specific shape through noncovalent interaction. Herein, we report the influence of β-CD complex formation of an Antipyrine derivative on its metal ion sensing behavior. In aqueous solution, the Antipyrine shows a turn-on fluorescence sensing of vanadyl ion, and in cyclodextrin medium it senses aluminum ion. The compound shows an unusual fluorescence quenching on binding with β-cyclodextrin (log KSV = 2.34 ± 0.02). The differential metal ion sensing is due to the partial blocking of the chelating moiety by the cyclodextrin molecule. The structure of the Antipyrine–cyclodextrin complex is optimized by two-dimensional rotating-frame Overhauser effect spectroscopy. The binding constant is determined by isothermal titration calorimetry (log K = 2.09 ± 0.004). The metal ion binding site is optimized by quanutm mechanical calculations. The lower limit of detection of vanadyl a...
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Differential Metal Ion Sensing by an Antipyrine Derivative in Aqueous and β‑Cyclodextrin Media: Selectivity Tuning by β‑Cyclodextrin
2018Co-Authors: Govindaraj Tamil Selvan, Sumathi Poomalai, Sivaraj Ramasamy, Paulraj Mosae Selvakumar, Sara Gracia Lanas, Israel Muthu Vijayan V Enoch, Andrea MelchiorAbstract:β-Cyclodextrin (β-CD) is a nontoxic cyclic oligosachcharide that can encapsulate all or part of organic molecules of appropriate size and specific shape through noncovalent interaction. Herein, we report the influence of β-CD complex formation of an Antipyrine derivative on its metal ion sensing behavior. In aqueous solution, the Antipyrine shows a turn-on fluorescence sensing of vanadyl ion, and in cyclodextrin medium it senses aluminum ion. The compound shows an unusual fluorescence quenching on binding with β-cyclodextrin (log KSV = 2.34 ± 0.02). The differential metal ion sensing is due to the partial blocking of the chelating moiety by the cyclodextrin molecule. The structure of the Antipyrine–cyclodextrin complex is optimized by two-dimensional rotating-frame Overhauser effect spectroscopy. The binding constant is determined by isothermal titration calorimetry (log K = 2.09 ± 0.004). The metal ion binding site is optimized by quanutm mechanical calculations. The lower limit of detection of vanadyl and aluminum ions, respectively, are 5 × 10–8 and 5 × 10–7 mol dm–3. This is the first report of selectivity of two different cations by a chemosensor in water and in β-CD
R Y Yeung - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the protective effects of schisandra chinensis on phase i drug metabolism using a ccl4 intoxication model
Journal of Ethnopharmacology, 1999Co-Authors: R Y Yeung, Rong LiAbstract:To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 damaged liver, Antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague–Dawley rats (220–240 g) 30 min or 6 h before CCl4 intoxication (4 ml/kg, s.c.). Following a single oral dose of Antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of Antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P450 were measured. Pharmacokinetic parameters for Antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 significantly increased the elimination half-life (t1/2) of Antipyrine from 2.59±1.04 to 11.25±3.91 h (P<0.001) and decreased its clearance (CL) from 65.94 to 10.84 ml/h as compared to control. Pretreatment with the Schisandra lignan fraction 30 min or 6 h before intoxication significantly (P<0.001) improved Antipyrine elimination by reducing its t1/2 to 3.30±0.52 and 3.58±1.05 h, respectively. The corresponding improvements observed for CL, i.e. 49.06±21.75 ml/h (P<0.01); 21.10±10.42 ml/h (P<0.05), were also substantial. Moreover, normalization of SGPT, SGOT and P450 levels was observed with the two Schisandra pretreatment schedules. In conclusion, Schisandra lignans exhibited strong protective effect on Phase I oxidative metabolism in the liver damaged by CCl4. Furthermore, pretreatment of Schisandra 30 min before intoxication showed a more pronounced effect than that of the 6 h pretreatment. The current pharmacokinetic approach allowed the protective effects of Schisandra on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the evaluation of hepato-protectants obtained from natural sources.
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evaluation of the protective effects of schisandra chinensis on phase i drug metabolism using a ccl4 intoxication model
Journal of Ethnopharmacology, 1999Co-Authors: Min Zhu, K F Lin, R Y YeungAbstract:Abstract To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 damaged liver, Antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague–Dawley rats (220–240 g) 30 min or 6 h before CCl4 intoxication (4 ml/kg, s.c.). Following a single oral dose of Antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of Antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P450 were measured. Pharmacokinetic parameters for Antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 significantly increased the elimination half-life (t1/2) of Antipyrine from 2.59±1.04 to 11.25±3.91 h (P
John H. Cavanaugh - One of the best experts on this subject based on the ideXlab platform.
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the effect of zileuton on Antipyrine and indocyanine green disposition
Clinical Pharmacology & Therapeutics, 1995Co-Authors: John V St Peter, Rene A Braeckman, Charles S Locke, Richard G Granneman, John H. CavanaughAbstract:The effects of single and multiple oral doses of zileuton on the pharmacokinetics of Antipyrine and indocyanine green were studied in 16 healthy, nonsmoking adult men by means of a double-blind, randomized, parallel placebo-controlled design. Indocyanine green disposition was not significantly altered by zileuton. Plasma Antipyrine clearance declined by 20% (p < 0.0005) and 52% (p < 0.0005) after single and multiple dose zileuton exposure, respectively. Total urinary recovery of unchanged Antipyrine and metabolites decreased with zileuton exposure. Selective declines from baseline of 16% (p = 0.007) and 20% (p = 0.003) after single-dose zileuton and 30% (p < 0.0005) and 43% (p < 0.0005) after multiple-dose zileuton were detected in recovery of 4-hydroxyAntipyrine and 3-hydroxymethylAntipyrine, respectively. Urinary recovery of the N-demethylAntipyrine metabolite norAntipyrine and percent of conjugation of 3-hydroxymethylAntipyrine were unchanged by zileuton. In conclusion, zileuton therapy has no detectable effect on indocyanine green disposition but exerts marked effects on Antipyrine plasma and urine metabolite disposition. Clinical Pharmacology & Therapeutics (1995) 57, 299–308; doi: