James B. Mangold

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Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a novel, chemically distinct cyclooxygenase-2 selective inhibitor, which has been developed for the treatment of osteoarthritis, rheumatoid arthritis, and acute pain. The absorption, metabolism, disposition, and mass balance of [14C]lumiracoxib were investigated in four(More)
The absorption, metabolism, and excretion of (1-[[3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine (vildagliptin), an orally active and highly selective dipeptidyl peptidase 4 inhibitor developed for the treatment of type 2 diabetes, were evaluated in four healthy male subjects after a single p.o. 100-mg dose of [(14)C]vildagliptin. Serial(More)
The pharmacokinetics and metabolism of nateglinide were studied in six healthy male subjects receiving a single oral (120 mg) and intravenous (60 mg) dose of [14C]nateglinide in randomized order. Serial blood and complete urine and feces were collected for 120 h post dose. Nateglinide was rapidly (approximately 90%) absorbed, with peak blood and plasma(More)
Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P(1)' site. Using a combination of iterative parallel(More)
Lumiracoxib (Prexige) is a selective cyclo-oxygenase (COX)-2 inhibitor developed for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. Lumiracoxib possesses a carboxylic acid group that makes it weakly acidic (acid dissociation constant [pKa] 4.7), distinguishing it from other selective COX-2 inhibitors. Lumiracoxib has good oral(More)
Alisporivir is a novel cyclophilin-binding molecule with potent anti-hepatitis C virus (HCV) activity. In vitro data from human liver microsomes suggest that alisporivir is a substrate and a time-dependent inhibitor (TDI) of CYP3A4. The aim of the current work was to develop a novel physiologically based pharmacokinetic (PBPK) model to quantitatively assess(More)
The pharmacokinetics and metabolism of cyclosporin G (CsG; Sandoz compound OG 37-325) were studied in 12 healthy male volunteers receiving a single oral dose of 150 or 600 mg of [14C]CsG. Serial blood and plasma samples and complete urine and feces were collected for 120-hr postdose. CsG was rapidly absorbed, and the extent of absorption was(More)
The absorption, metabolism, and excretion of (1-[[3-hydroxy-1adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine (vildagliptin), an orally active and highly selective dipeptidyl peptidase 4 inhibitor developed for the treatment of type 2 diabetes, were evaluated in four healthy male subjects after a single p.o. 100-mg dose of [C]vildagliptin. Serial blood and(More)
1. Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor (ARNI) providing simultaneous inhibition of neprilysin (neutral endopeptidase 24.11; NEP) and blockade of the angiotensin II type-1 (AT1) receptor. 2. Following oral administration, [(14)C]LCZ696 delivers systemic exposure to valsartan and AHU377 (sacubitril), which is rapidly(More)
Epothilones are natural macrolides displaying potent antiproliferative properties against various cell lines and capable to bind tubulin and acting as microtubule-stabilizing agents like taxoids. We intended to isolate and characterize epothilone metabolites and identify enzymes implicated in the biotransformation process. In the presence of NADPH, liver(More)