Metabolism And Excretion of the Dipeptidyl Peptidase 4 Inhibitor [14C]Sitagliptin in Humans
Citations
475 citations
Cites background from "Metabolism And Excretion of the Dip..."
...Three of these metabolites (M1, M2 and M5) are active, but are not expected to contribute to the pharmacodynamic profile of sitagliptin because of the combination of low plasma concentration and low affinity for DPP-4 [8,9]....
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...For sitagliptin, the limited metabolism produces six metabolites in trace amounts (each accounting for <1% to 7% of sitagliptin-related material in plasma), with in vitro studies indicating that the primary enzyme responsible is CYP3A4 with a lesser contribution from CYP2C8 [8]....
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255 citations
Cites background or methods from "Metabolism And Excretion of the Dip..."
...tablet of sitagliptin administered following a high-fat meal, and a single oral 100-mg sitagliptin administered fasted [29]....
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...The metabolism and excretion of 14C-sitagliptin were investigated in humans after a single oral dose of 83 mg/193 muCi [29]....
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...Because sitagliptin is primarily excreted by renal elimination as unchanged drug, with only a small percentage (approximately 16%) undergoing hepatic metabolism [29], one may hypothesize that sitagliptin could be safely used in patients with mild to moderate hepatic impairment....
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197 citations
Cites background from "Metabolism And Excretion of the Dip..."
...Following the administration of a single dose, approximately 87% of sitagliptin [13], 75% of saxagliptin [14] and 85% of vildagliptin (not currently approved in the United States) [15,16] are excreted in the urine....
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196 citations
185 citations
Cites background from "Metabolism And Excretion of the Dip..."
...…al., 2009; Scheen, 2010 Sitagliptin Januvia1 DPP4 inhibitor 8–14 h Low Renal Baggio and Drucker, 2007; Chu et al., 2007; Deacon, 2011; Herman et al., 2005; Vincent et al., 2007 Vildagliptin Galvus1 DPP4 inhibitor 2–3 h Low Renal Baggio and Drucker, 2007; Deacon, 2011; EMEA, 2007; He et al., 2009;…...
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...P-1 signaling in neurodegenerative disorders: Targets for disease eurobio.2014.02.005 F. Bassil et al. / Progress in Neurobiology xxx (2014) xxx–xxx 5 Drug Trade name Function Half-life BBB penetration Excretion Tissue distribution References Albiglutide Syncria1 GLP-1 Analog 6–8 days None to very limited No data GLP-1 binding sites: kidney, lung, pancreas, stomach, blood, spleen, liver and brain Baggio et al., 2004; Bush et al., 2009; Rosenstock et al., 2009 Exendin-4 Byetta1 Bydureon1 GLP-1 analog 2–3 h High Renal Copley et al., 2006; EMEA, 2009a, 2010; Kastin and Akerstrom, 2003; Wild et al., 2010 Liraglutide Victoza1 GLP-1 analog 4–15 h Moderate to high None Elbrond et al., 2002; Hunter and Holscher, 2012; Malm-Erjefalt et al., 2010; McClean et al., 2010 Lixisenatide Lyxumia1 GLP-1 analog 2–4 h Moderate to high Renal EMEA, 2013; Hunter and Holscher, 2012 Alogliptin Nesina1 DPP4 inhibitor 12–21 h No data Renal Kidney, lung, liver, intestine, adrenal gland, testis, pancreas, spleen; low amounts in brain; Surface of endothelial cells lining blood vessels and found in a soluble form, freely circulating in the blood Baetta and Corsini, 2011; Baggio and Drucker, 2007; Christopher et al., 2008; Scheen, 2010 Linagliptin Tranjenta1 DPP4 inhibitor 36 h Low Fecal Baggio and Drucker, 2007; Blech et al., 2010; Deacon, 2011; EMEA, 2011; Fuchs et al., 2009; Scheen, 2010 Saxagliptin Onglyza1 DPP4 inhibitor 2–4 h Low Renal Baggio and Drucker, 2007; Deacon, 2011; EMEA, 2009b; Fura et al., 2009; Scheen, 2010 Sitagliptin Januvia1 DPP4 inhibitor 8–14 h Low Renal Baggio and Drucker, 2007; Chu et al., 2007; Deacon, 2011; Herman et al., 2005; Vincent et al., 2007 Vildagliptin Galvus1 DPP4 inhibitor 2–3 h Low Renal Baggio and Drucker, 2007; Deacon, 2011; EMEA, 2007; He et al., 2009; Scheen, 2010...
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References
1,308 citations
"Metabolism And Excretion of the Dip..." refers background in this paper
...GLP-1, which is released upon nutrient ingestion, stimulates meal-induced insulin secretion and contributes to glucose homeostasis (Kieffer and Habener, 1999)....
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823 citations
"Metabolism And Excretion of the Dip..." refers background in this paper
...1), is an orally active, potent and selective DPP-4 inhibitor with an IC50 value of 18 nM (Kim et al., 2005)....
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490 citations
"Metabolism And Excretion of the Dip..." refers background or result in this paper
...These data are corroborated by 537[14C]SITAGLIPTIN HUMAN ADME the high bioavailability (Bergman et al., 2005) and high recovery of parent drug in urine after the administration of unlabeled sitagliptin to healthy subjects (Herman et al., 2005a; Bergman et al., 2006)....
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...Sitagliptin has been shown to inhibit plasma DPP-4 activity in a dose-dependent manner and to enhance active GLP-1 levels in normal volunteers (Bergman et al., 2005, 2006; Herman et al., 2005b) and patients with type 2 diabetes (Herman et al., 2004)....
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...…insulin and C-peptide release, decreased glucagon secretion, and reduced plasma glucose levels after an oral glucose tolerance test (Herman et al., 2004), whereas 12-week treatment with sitagliptin significantly reduced HbA1c and fasting plasma glucose (Herman et al., 2005a; Scott et al., 2005)....
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298 citations
"Metabolism And Excretion of the Dip..." refers background in this paper
...Dipeptidyl peptidase 4 (DPP-4) is a ubiquitous proline-specific serine protease responsible for the rapid inactivation of incretins, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (Gorrell, 2005)....
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261 citations
"Metabolism And Excretion of the Dip..." refers background or methods or result in this paper
...Concentrations of sitagliptin in plasma were determined by direct on-line LC-MS/MS analysis using a Cohesive Technologies (Franklin, MA) high turbulence liquid chromatography system, as described in more detail elsewhere (Bergman et al., 2006)....
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...These data are corroborated by 537[14C]SITAGLIPTIN HUMAN ADME the high bioavailability (Bergman et al., 2005) and high recovery of parent drug in urine after the administration of unlabeled sitagliptin to healthy subjects (Herman et al., 2005a; Bergman et al., 2006)....
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...Sitagliptin has been shown to inhibit plasma DPP-4 activity in a dose-dependent manner and to enhance active GLP-1 levels in normal volunteers (Bergman et al., 2005, 2006; Herman et al., 2005b) and patients with type 2 diabetes (Herman et al., 2004)....
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