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Identification of the Human Cytochrome P450 Enzymes Involved in the Two Oxidative Steps in the Bioactivation of Clopidogrel to Its Pharmacologically Active Metabolite
TLDR
Identifying the human cytochrome P450 isoforms involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite helped explain the role of genetic polymorphism of CYP2C19 and also the effect of potent CYP3A inhibitors on the pharmacokinetics and pharmacodynamics of clopsinogrel in humans and on clinical outcomes.
Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro.
TLDR
Sertraline N-demethylation activities were detected in all cDNA-expressed CYP isoforms studied and that the contribution of any individual isoform does not exceed 40% of overall metabolism is suggested.
Human Carboxymethylenebutenolidase as a Bioactivating Hydrolase of Olmesartan Medoxomil in Liver and Intestine
TLDR
It is reported for the first time that CMBL serves as a key enzyme in the bioactivation of OM, hydrolyzing the ester bond of the prodrug type xenobiotics.
Use of an intravenous microdose of 14C-labeled drug and accelerator mass spectrometry to measure absolute oral bioavailability in dogs; cross-comparison of assay methods by accelerator mass
TLDR
On utilizing simultaneous intravenous microdosing of (14)C-labeled drug in conjunction with AMS analysis, absolute bioavailability could be approximately measured in dogs, but without total accuracy.
Distribution of KAI-9803, a Novel δ-Protein Kinase C Inhibitor, after Intravenous Administration to Rats
TLDR
It is demonstrated that after a single intravenous administration, KAI-9803 can be delivered into the target cells in the liver, kidney, and heart by a TAT47–57-mediated mechanism.
Different Hydrolases Involved in Bioactivation of Prodrug-Type Angiotensin Receptor Blockers: Carboxymethylenebutenolidase and Carboxylesterase 1
TLDR
Comparing the bioactivating properties of OM with those of other prodrug-type ARBs, candesartan cilexetil (CC) and azilsartan medoxomil (AM), by focusing on interspecies differences and tissue specificity, concludes that OM is bioactivated mainly via intestinal and additionally hepatic CMBL not only in humans but also in mice, rats, and monkeys.
In vivo multiple metabolic pathways for a novel G protein-coupled receptor 119 agonist DS-8500a in rats: involvement of the 1,2,4-oxadiazole ring-opening reductive reaction in livers under anaerobic
TLDR
An in vivo unique reductive metabolism of DS-8500a is mediated by human non-cytochrome P450 enzymes, and extensive formation of the ring-opened metabolites was observed in human liver microsomes fortified with an NADPH-generating system under anaerobic conditions.
A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors
TLDR
Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients, and one patient with tenosynovial giant cell tumor showed objective tumor response.
Paraoxonase 1 as a Major Bioactivating Hydrolase for Olmesartan Medoxomil in Human Blood Circulation: Molecular Identification and Contribution to Plasma Metabolism
TLDR
PON1 is identified as the OM-bioactivating hydrolase in human plasma on a molecular basis and it is demonstrated that PON1, but not albumin, plays a major role in OM bioactivation inhuman plasma.
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