The Experts below are selected from a list of 427131 Experts worldwide ranked by ideXlab platform
Nina Isoherranen - One of the best experts on this subject based on the ideXlab platform.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal drug excretion and systemic drug disposition has been observed for many drugs. When urine pH is altered, tubular drug ionization, passive reabsorption, renal clearance, and systemic exposure may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that PBPK modeling can be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full body PBPK model to simulate renal clearance and systemic AUC with varying urine pH statuses, using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition (absolute-average-fold-error (AAFE) < 1.25 at study level). Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full body PBPK model also successfully simulated ampHetamine plasma concentration-time profile (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratio (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full body PBPK model can predict the magnitude of alteration in renal excretion and systemic AUC of drugs when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important as multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) < 1.25 at study level]. Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full-body PBPK model also successfully simulated ampHetamine plasma concentration-time profiles (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratios (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of MethampHetamine and AmpHetamine.
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) SIGNIFICANCE STATEMENT Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
Lian Gao - One of the best experts on this subject based on the ideXlab platform.
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pH Effect on titania pHase transformation of precipitates from titanium tetrachloride solutions
Journal of the American Ceramic Society, 2002Co-Authors: Jing Sun, Lian GaoAbstract:Precipitates in different structures were prepared by the hydrolysis of a TiCl4 solution at room temperature and 70°C. The pH Effect on titania-pHase transformation was investigated. The original precipitate formed by the hydrolysis of titanium tetrachloride formed a gel-like structure at pH 4 with the addition of NH4OH, which could be changed to essentially 100% rutile pHase at 600°C. The rutile precipitates prepared at 70°C could be changed to mixed-pHase product at pH 0.50 and total anatase pHase at pH 3.13 and 5.15. Complete pHase transformation from anatase to rutile occurred in the three samples at 700°C.
Weize Huang - One of the best experts on this subject based on the ideXlab platform.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal drug excretion and systemic drug disposition has been observed for many drugs. When urine pH is altered, tubular drug ionization, passive reabsorption, renal clearance, and systemic exposure may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that PBPK modeling can be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full body PBPK model to simulate renal clearance and systemic AUC with varying urine pH statuses, using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition (absolute-average-fold-error (AAFE) < 1.25 at study level). Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full body PBPK model also successfully simulated ampHetamine plasma concentration-time profile (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratio (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full body PBPK model can predict the magnitude of alteration in renal excretion and systemic AUC of drugs when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important as multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) < 1.25 at study level]. Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full-body PBPK model also successfully simulated ampHetamine plasma concentration-time profiles (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratios (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of MethampHetamine and AmpHetamine.
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) SIGNIFICANCE STATEMENT Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
Jing Sun - One of the best experts on this subject based on the ideXlab platform.
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pH Effect on titania pHase transformation of precipitates from titanium tetrachloride solutions
Journal of the American Ceramic Society, 2002Co-Authors: Jing Sun, Lian GaoAbstract:Precipitates in different structures were prepared by the hydrolysis of a TiCl4 solution at room temperature and 70°C. The pH Effect on titania-pHase transformation was investigated. The original precipitate formed by the hydrolysis of titanium tetrachloride formed a gel-like structure at pH 4 with the addition of NH4OH, which could be changed to essentially 100% rutile pHase at 600°C. The rutile precipitates prepared at 70°C could be changed to mixed-pHase product at pH 0.50 and total anatase pHase at pH 3.13 and 5.15. Complete pHase transformation from anatase to rutile occurred in the three samples at 700°C.
Lindsay C Czuba - One of the best experts on this subject based on the ideXlab platform.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal drug excretion and systemic drug disposition has been observed for many drugs. When urine pH is altered, tubular drug ionization, passive reabsorption, renal clearance, and systemic exposure may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that PBPK modeling can be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full body PBPK model to simulate renal clearance and systemic AUC with varying urine pH statuses, using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition (absolute-average-fold-error (AAFE) < 1.25 at study level). Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full body PBPK model also successfully simulated ampHetamine plasma concentration-time profile (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratio (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full body PBPK model can predict the magnitude of alteration in renal excretion and systemic AUC of drugs when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important as multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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mechanistic pbpk modeling of urine pH Effect on renal and systemic disposition of methampHetamine and ampHetamine
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) < 1.25 at study level]. Then, acidic and alkaline urine scenarios were simulated. Our simulation results show that the renal excretion and plasma concentration-time profiles for methampHetamine and ampHetamine could be recapitulated under different urine pH (AAFE < 2 at individual level). The methampHetamine-ampHetamine parent-metabolite full-body PBPK model also successfully simulated ampHetamine plasma concentration-time profiles (AAFE < 1.25 at study level) and ampHetamine/methampHetamine urinary concentration ratios (AAFE < 2 at individual level) after dosing methampHetamine. This demonstrates that our mechanistic PBPK model can predict urine pH Effect on systemic and urinary disposition of drugs and metabolites. SIGNIFICANCE STATEMENT: Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.
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Mechanistic PBPK Modeling of Urine pH Effect on Renal and Systemic Disposition of MethampHetamine and AmpHetamine.
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Weize Huang, Lindsay C Czuba, Nina IsoherranenAbstract:The Effect of urine pH on renal excretion and systemic disposition has been observed for many drugs and metabolites. When urine pH is altered, tubular ionization, passive reabsorption, renal clearance, and systemic exposure of drugs and metabolites may all change dramatically, raising clinically significant concerns. Surprisingly, the urine pH Effect on drug disposition is not routinely explored in humans, and regulatory agencies have neither developed guidance on this issue nor required industry to conduct pertinent human trials. In this study, we hypothesized that pHysiologically based pHarmacokinetic (PBPK) modeling could be used as a cost-Effective method to examine potential urine pH Effect on drug and metabolite disposition. Our previously developed and verified mechanistic kidney model was integrated with a full-body PBPK model to simulate renal clearance and area under the plasma concentration-time curve (AUC) with varying urine pH statuses using methampHetamine and ampHetamine as model compounds. We first developed and verified drug models for methampHetamine and ampHetamine under normal urine pH condition [absolute average fold error (AAFE) SIGNIFICANCE STATEMENT Our study shows that integrating mechanistic kidney model with full-body pHysiologically based pHarmacokinetic model can predict the magnitude of alteration in renal excretion and area under the plasma concentration-time curve (AUC) of drugs and metabolites when urine pH is changed. This provides a cost-Effective method to evaluate the likelihood of renal and systemic disposition changes due to varying urine pH. This is important because multiple drugs and diseases can alter urine pH, leading to quantitatively and clinically significant changes in drug and metabolite disposition that may require adjustment of therapy.