Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective
Xenobiotica. 2023 Oct 25:1-12. doi: 10.1080/00498254.2023.2272180. Online ahead of print.ABSTRACT1. Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study.2. Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2. Ratio of the enantiomers was determined by enantioselective liq...
Source: Xenobiotica - October 26, 2023 Category: Research Authors: Holger Scheible Hanno Schieferstein Ralf Schmidt Klaus Pusecker Ulrike Gradhand Sathej Gopalakrishnan Khalid Iqbal Jennifer Dong Reinaldo Jones Claudia Meli Jayaprakasam Bolleddula Martin Dyroff Katrin Georgi Source Type: research
Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective
Xenobiotica. 2023 Oct 25:1-12. doi: 10.1080/00498254.2023.2272180. Online ahead of print.ABSTRACT1. Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple sclerosis. One major circulating metabolite of evobrutinib has been previously identified as the racemic dihydro-diol M463-2 (MSC2430422) in a Phase I human mass balance study.2. Phenotyping experiments were conducted to confirm the metabolic pathway of evobrutinib to M463-2. Ratio of the enantiomers was determined by enantioselective liq...
Source: Xenobiotica - October 26, 2023 Category: Research Authors: Holger Scheible Hanno Schieferstein Ralf Schmidt Klaus Pusecker Ulrike Gradhand Sathej Gopalakrishnan Khalid Iqbal Jennifer Dong Reinaldo Jones Claudia Meli Jayaprakasam Bolleddula Martin Dyroff Katrin Georgi Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS
This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.PMID:37850428 | DOI:10.1080/00498254.2023.2272193 (Source: Xenobiotica)
Source: Xenobiotica - October 18, 2023 Category: Research Authors: Yuxuan Fan Yufeng Ni Minlu Cheng Wenjing Guo Huaye Gao WenHui Hu Chang Shu Li Ding Source Type: research
Evaluation of the non-linearity of NA808 in liver not reflected in plasma using a rat pharmacokinetic study and PBPK modelling
Xenobiotica. 2023 Oct 17:1-9. doi: 10.1080/00498254.2023.2267107. Online ahead of print.ABSTRACTWhen NA808, a potent HCV replication inhibitor, was intravenously administered to rats, it was distributed to the liver. The AUC ratio in the liver of 20 mg/kg to 2 mg/kg was greater than the dose ratio, whereas exposure in plasma was increased in a dose-proportional manner. Saturation of biliary excretion was also shown at 20 mg/kg.NA808 was revealed to be a substrate for both OATP1B and MRP2 transporters by an in vitro study using OATP1B1-MRP2 expressing cells. [14C]NA808 was taken up into the cells by OATP1B1 and excreted fro...
Source: Xenobiotica - October 17, 2023 Category: Research Authors: Mizuki Yamane Kazuhisa Ozeki Ken Okano Toshiyuki Kudo Kiyomi Ito Source Type: research
Evaluation of the non-linearity of NA808 in liver not reflected in plasma using a rat pharmacokinetic study and PBPK modelling
Xenobiotica. 2023 Oct 17:1-9. doi: 10.1080/00498254.2023.2267107. Online ahead of print.ABSTRACTWhen NA808, a potent HCV replication inhibitor, was intravenously administered to rats, it was distributed to the liver. The AUC ratio in the liver of 20 mg/kg to 2 mg/kg was greater than the dose ratio, whereas exposure in plasma was increased in a dose-proportional manner. Saturation of biliary excretion was also shown at 20 mg/kg.NA808 was revealed to be a substrate for both OATP1B and MRP2 transporters by an in vitro study using OATP1B1-MRP2 expressing cells. [14C]NA808 was taken up into the cells by OATP1B1 and excreted fro...
Source: Xenobiotica - October 17, 2023 Category: Research Authors: Mizuki Yamane Kazuhisa Ozeki Ken Okano Toshiyuki Kudo Kiyomi Ito Source Type: research
Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from < em > Uncaria rhynchophylla < /em >
This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.PMID:37819730 | DOI:10.1080/00498254.2023.2269417 (Source: Xenobiotica)
Source: Xenobiotica - October 11, 2023 Category: Research Authors: Yiqing Guo Huanhuan Lv Jing Lv Zenghong Jiang Source Type: research
Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from < em > Uncaria rhynchophylla < /em >
This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.PMID:37819730 | DOI:10.1080/00498254.2023.2269417 (Source: Xenobiotica)
Source: Xenobiotica - October 11, 2023 Category: Research Authors: Yiqing Guo Huanhuan Lv Jing Lv Zenghong Jiang Source Type: research
Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla
This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.PMID:37819730 | DOI:10.1080/00498254.2023.2269417 (Source: Xenobiotica)
Source: Xenobiotica - October 11, 2023 Category: Research Authors: Yiqing Guo Huanhuan Lv Jing Lv Zenghong Jiang Source Type: research
Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla
This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.PMID:37819730 | DOI:10.1080/00498254.2023.2269417 (Source: Xenobiotica)
Source: Xenobiotica - October 11, 2023 Category: Research Authors: Yiqing Guo Huanhuan Lv Jing Lv Zenghong Jiang Source Type: research
Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla
This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.PMID:37819730 | DOI:10.1080/00498254.2023.2269417 (Source: Xenobiotica)
Source: Xenobiotica - October 11, 2023 Category: Research Authors: Yiqing Guo Huanhuan Lv Jing Lv Zenghong Jiang Source Type: research
