The metabolism and disposition of fenofibrate in rat, guinea pig, and dog.
- Authors
- Weil, A; Caldwell, J; Strolin-Benedetti, M
- Year
- 1988
- Journal
- Drug metabolism and disposition: the biological fate of chemicals
- PMID
- 2898351
The metabolism and disposition of orally administered single doses of [14C]fenofibrate (isopropyl 2-[4-(4-chlorobenzoyl)phenoxy]-2- methylpropionate) have been studied in rat, guinea pig, and dog. In rats, the urinary excretion of 14C in 5 days varied from 11 to 51% of the dose and was markedly dependent upon the dose form given. The interpretation of these data in terms of factors affecting the absorption of fenofibrate from the gut is complicated by the enterohepatic recirculation of metabolites. The tissue distribution of 14C after oral administration of an ethanolic solution of fenofibrate has been studied in the rat. The only tissues in which the concentration of 14C exceeded that in the blood were the organs of absorption and elimination, the gut, liver, and kidneys. Guinea pigs excreted 53% of the dose in the urine in 5 days, with a further 34% in the feces, while in dogs the corresponding figures were 9% and 81%, respectively. In all three species, all the urinary metabolites were products of ester hydrolysis, and the principal excretion product was "reduced fenofibric acid" which arose by subsequent carbonyl reduction. Glucuronidation of fenofibric acid and "reduced fenofibric acid" was a very minor reaction in the rat and guinea pig and was not detected in the dog. In addition, polar unknown metabolite(s) were detected in all three species, but were not investigated further. The results are discussed in terms of the comparative disposition of fenofibrate and other hypolipidemic agents and the contribution of these findings to the safety assessment of such drugs.
No figures extracted from this document.
No chunks โ full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Peroxisome proliferator-activated receptors ฮฑ and ฮณ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | 2015 | 25516156 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Quantifying In Vivo Luminal Drug Solubilization -Supersaturation-Precipitation Profiles to Explain the Performance of Lipid Based Formulations. | Tanaka Y et al. | โ | 2020 | โ |
| Pharmacokinetics and metabolism of pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator, in rats and monkeys. | Ogawa SI et al. | โ | 2019 | โ |
| Testing the PPAR hypothesis of tobacco use disorder in humans: A randomized trial of the impact of gemfibrozil (a partial PPARฮฑ agonist) in smokers. | Gendy MNS et al. | โ | 2018 | โ |
| Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels. | Rivera-Meza M et al. | โ | 2017 | โ |
| A new in vitro lipid digestion - in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations. | Crum MF et al. | โ | 2016 | โ |
| Fenofibrate subcellular distribution as a rationale for the intracranial delivery through biodegradable carrier. | Grabacka M et al. | โ | 2015 | โ |
| Peroxisome proliferator-activated receptors ฮฑ and ฮณ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | Blednov YA et al. | โ | 2015 | โ |
| Carbonyl reduction pathways in drug metabolism. | Malรกtkovรก P et al. | โ | 2014 | โ |
| In vitro lipolysis data does not adequately predict the in vivo performance of lipid-based drug delivery systems containing fenofibrate. | Thomas N et al. | โ | 2014 | โ |
| A novel prodrug strategy for extremely hydrophobic agents: conjugation to symmetrically branched glycerol trimer improves pharmacological and pharmacokinetic properties of fenofibrate. | Miyamoto L et al. | โ | 2013 | โ |
| Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress. | Hiyama Y et al. | โ | 2013 | โ |
| Premature drug release of polymeric micelles and its effects on tumor targeting. | Miller T et al. | โ | 2013 | โ |
| Soluplusยฎ as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. | Linn M et al. | โ | 2012 | โ |
| Xenobiotic metabolomics: major impact on the metabolome. | Johnson CH et al. | โ | 2012 | โ |
| Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPARฮฑ-dependent and -independent pathways. | Goto T et al. | โ | 2011 | โ |
| The conflict between in vitro release studies in human biorelevant media and the in vivo exposure in rats of the lipophilic compound fenofibrate. | Do TT et al. | โ | 2011 | โ |
| Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. | Van Speybroeck M et al. | โ | 2010 | โ |
| Fenofibrate-loaded PLGA microparticles: effects on ischemic stroke. | Klose D et al. | โ | 2009 | โ |
| Fenofibrate metabolism in the cynomolgus monkey using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics. | Liu A et al. | โ | 2009 | โ |
| New metabolites of fenofibrate in Sprague-Dawley rats by UPLC-ESI-QTOF-MS-based metabolomics coupled with LC-MS/MS. | Liu A et al. | โ | 2009 | โ |
| An automated method for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite, pravalactone and fenofibric acid in human plasma by sensitive liquid chromatography combined with diode array and tandem mass spectrometry detection. | Mertens B et al. | โ | 2008 | โ |
| Antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPAR alpha, and pioglitazone, an agonist of PPAR gamma. | Oliveira AC et al. | โ | 2007 | โ |
| The PPAR-alpha activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs. | Xu Y et al. | โ | 2006 | โ |
| Enhancement of oral bioavailability of poorly water-soluble drugs by poly(ethylene glycol)-block-poly(alkyl acrylate-co-methacrylic acid) self-assemblies. | Sant VP et al. | โ | 2005 | โ |
| Fenofibrate and fenofibric acid analysis by capillary electrophoresis. | Shihabi ZK | โ | 2004 | โ |
| The biochemistry of hypo- and hyperlipidemic fatty acid derivatives: metabolism and metabolic effects. | Bremer J | โ | 2001 | โ |
| Determination of fenofibric acid in human plasma using automated solid-phase extraction coupled to liquid chromatography. | Streel B et al. | โ | 2000 | โ |
| Distribution of fenofibric acid in lipoprotein fractions of patients. | Nobilis M et al. | โ | 1998 | โ |
| The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. | Clifford AJ et al. | โ | 1998 | โ |
| An introduction to drug disposition: the basic principles of absorption, distribution, metabolism, and excretion. | Caldwell J et al. | โ | 1995 | โ |
| An experimental design strategy for quantitating complex pharmacokinetic models: enterohepatic circulation with time-varying gallbladder emptying as an example. | Wang YM et al. | โ | 1992 | โ |
| Fenofibrate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in dyslipidaemia. | Balfour JA et al. | โ | 1990 | โ |
| Species differences in the chirality of the carbonyl reduction of [14C] fenofibrate in laboratory animals and humans. | Weil A et al. | โ | 1989 | โ |