ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
ADME properties of CHF6366, a novel bi-functional M3-Muscarinic receptor antagonist and ß-2 adrenoceptor agonist (MABA) radiolabeled at both functional moieties
Xenobiotica. 2023 Jun 27:1-59. doi: 10.1080/00498254.2023.2230490. Online ahead of print.ABSTRACTCHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD), was [14C]-radiolabeled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterize its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration.A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution th...
Source: Xenobiotica - June 28, 2023 Category: Research Authors: A Ghiglieri M Messina V Cenacchi C Piutti F Cinato G Brogin P Puccini Source Type: research
Determination of enzymatic kinetics of metabolism of dimethoate and omethoate in rats and humans
The objective of this work was to determine the enzymatic kinetics of metabolism of dimethoate and its active metabolite omethoate in rats and humans and obtain key input parameters for physiologically based pharmacokinetic (PBPK) model.2. First, the intrinsic clearance of dimethoate expressed as formation rate of omethoate was determined to be ∼42-fold lower in human liver microsomes (HLM) (0.39 µL/min/mg) than in rat liver microsomes (RLM) (16.6 µL/min/mg) by an LC/MS/MS method. Next, dimethoate clearance in liver microsomes was determined using parent depletion and total [14C]-metabolite formation methods. Results f...
Source: Xenobiotica - June 22, 2023 Category: Research Authors: Gopinath Nallani Appavu Chandrasekaran Kelem Kassahun Li Shen Rick Reiss Paul Whatling Source Type: research
Determination of enzymatic kinetics of metabolism of dimethoate and omethoate in rats and humans
The objective of this work was to determine the enzymatic kinetics of metabolism of dimethoate and its active metabolite omethoate in rats and humans and obtain key input parameters for physiologically based pharmacokinetic (PBPK) model.2. First, the intrinsic clearance of dimethoate expressed as formation rate of omethoate was determined to be ∼42-fold lower in human liver microsomes (HLM) (0.39 µL/min/mg) than in rat liver microsomes (RLM) (16.6 µL/min/mg) by an LC/MS/MS method. Next, dimethoate clearance in liver microsomes was determined using parent depletion and total [14C]-metabolite formation methods. Results f...
Source: Xenobiotica - June 22, 2023 Category: Research Authors: Gopinath Nallani Appavu Chandrasekaran Kelem Kassahun Li Shen Rick Reiss Paul Whatling Source Type: research
Determination of enzymatic kinetics of metabolism of dimethoate and omethoate in rats and humans
The objective of this work was to determine the enzymatic kinetics of metabolism of dimethoate and its active metabolite omethoate in rats and humans and obtain key input parameters for physiologically based pharmacokinetic (PBPK) model.2. First, the intrinsic clearance of dimethoate expressed as formation rate of omethoate was determined to be ∼42-fold lower in human liver microsomes (HLM) (0.39 µL/min/mg) than in rat liver microsomes (RLM) (16.6 µL/min/mg) by an LC/MS/MS method. Next, dimethoate clearance in liver microsomes was determined using parent depletion and total [14C]-metabolite formation methods. Results f...
Source: Xenobiotica - June 22, 2023 Category: Research Authors: Gopinath Nallani Appavu Chandrasekaran Kelem Kassahun Li Shen Rick Reiss Paul Whatling Source Type: research
Determination of enzymatic kinetics of metabolism of dimethoate and omethoate in rats and humans
The objective of this work was to determine the enzymatic kinetics of metabolism of dimethoate and its active metabolite omethoate in rats and humans and obtain key input parameters for physiologically based pharmacokinetic (PBPK) model.2. First, the intrinsic clearance of dimethoate expressed as formation rate of omethoate was determined to be ∼42-fold lower in human liver microsomes (HLM) (0.39 µL/min/mg) than in rat liver microsomes (RLM) (16.6 µL/min/mg) by an LC/MS/MS method. Next, dimethoate clearance in liver microsomes was determined using parent depletion and total [14C]-metabolite formation methods. Results f...
Source: Xenobiotica - June 22, 2023 Category: Research Authors: Gopinath Nallani Appavu Chandrasekaran Kelem Kassahun Li Shen Rick Reiss Paul Whatling Source Type: research
Determination of enzymatic kinetics of metabolism of dimethoate and omethoate in rats and humans
The objective of this work was to determine the enzymatic kinetics of metabolism of dimethoate and its active metabolite omethoate in rats and humans and obtain key input parameters for physiologically based pharmacokinetic (PBPK) model.2. First, the intrinsic clearance of dimethoate expressed as formation rate of omethoate was determined to be ∼42-fold lower in human liver microsomes (HLM) (0.39 µL/min/mg) than in rat liver microsomes (RLM) (16.6 µL/min/mg) by an LC/MS/MS method. Next, dimethoate clearance in liver microsomes was determined using parent depletion and total [14C]-metabolite formation methods. Results f...
Source: Xenobiotica - June 22, 2023 Category: Research Authors: Gopinath Nallani Appavu Chandrasekaran Kelem Kassahun Li Shen Rick Reiss Paul Whatling Source Type: research
An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MS < sup > E < /sup >
Xenobiotica. 2023 Jun 19:1-29. doi: 10.1080/00498254.2023.2227976. Online ahead of print.ABSTRACT1. Compound Kushen injection (CKI) is a kind of sterilized water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for nineteen years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.2. An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine and feces based on ultra-high performance liquid chromatography-ele...
Source: Xenobiotica - June 19, 2023 Category: Research Authors: Li Zhang Ruijuan Li Ting Zheng Huan Wu Yanyan Yin Source Type: research
An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MS < sup > E < /sup >
Xenobiotica. 2023 Jun 19:1-29. doi: 10.1080/00498254.2023.2227976. Online ahead of print.ABSTRACT1. Compound Kushen injection (CKI) is a kind of sterilized water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for nineteen years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.2. An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine and feces based on ultra-high performance liquid chromatography-ele...
Source: Xenobiotica - June 19, 2023 Category: Research Authors: Li Zhang Ruijuan Li Ting Zheng Huan Wu Yanyan Yin Source Type: research
