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Absorption, metabolism, and excretion of oral [C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.
Cancer Chemother Pharmacol
December 2024
Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, 215031, China.
Purpose: The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.
Methods: Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.
Human Mass Balance and Metabolite Profiling of [ C]-Pamiparib, a Poly (ADP-Ribose) Polymerase Inhibitor, in Patients With Advanced Cancer.
Clin Pharmacol Drug Dev
September 2021
BeiGene USA, Inc., San Mateo, California, USA.
Pamiparib, a selective poly (ADP-ribose) polymerase 1/2 inhibitor, demonstrated tolerability and antitumor activity in patients with solid tumors at 60 mg orally twice daily. This phase 1 open-label study (NCT03991494; BGB-290-106) investigated the absorption, metabolism, and excretion (AME) of 60 mg [ C]-pamiparib in 4 patients with solid tumors. The mass balance in excreta, blood, and plasma radioactivity and plasma pamiparib concentration were determined along with metabolite profiles in plasma, urine, and feces.
View Article and Find Full Text PDFNephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats.
Int J Mol Sci
December 2020
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0-1.5 mM; up to 90 min) or vehicle.
View Article and Find Full Text PDFMetabolism, Excretion and Pharmacokinetics of MLN3897, a CCR1 Antagonist, in Humans.
Drug Metab Lett
December 2016
Department of Metabolism and Pharmacokinetics, Takeda Pharmaceuticals Inc. Cambridge, MA 02139..
Unlabelled: MLN3897 is a small molecule antagonist of the C-C chemokine receptor-1. Since preclinical studies showed that the molecule was metabolized into two halves, the metabolism, excretion, and pharmacokinetics of MLN3897 were investigated in humans using MLN3897 14C-radiolabeled either on the chlorophenyl (CP) or the tricyclic (TC) half of MLN3897 after an oral dose.
Objective: To evaluate the mass balance, metabolism and pharmacokinetics of MLN3897 in two cohorts of six randomized healthy subjects.
Species-dependent metabolism of a novel selective α7 neuronal acetylcholine receptor agonist ABT-107.
Xenobiotica
September 2013
Department of Drug Metabolism and Pharmacokinetics, AbbVie, Inc., North Chicago, IL 60064, USA.
Metabolism of ABT-107 was investigated in in vitro hepatic systems, in rat and monkey receiving [¹⁴C]ABT-107, and in vivo plasma in rat, dog, monkey and human. In in vitro hepatic systems, ABT-107 was primarily cleared via oxidative metabolism, and proceeded via two parallel pathways. Pathway 1, ABT-107 was oxidized at the nitrogen of quinuclidine moiety to form M1.
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