PMID: 6678312Dec 1, 1983Paper

Evaluation of potential causes for the incomplete bioavailability of furosemide: gastric first-pass metabolism

Journal of Pharmacokinetics and Biopharmaceutics
M G Lee, W L Chiou

Abstract

Potential causes for reported incomplete (usually 40-60%) and often highly variable (e.g., 11-79%) bioavailability of furosemide in humans were investigated. The drug was found to be fairly stable in gastric fluids and its hepatic first-pass elimination (HFPE) was estimated to be much less than 6% based on published i.v. data. The rat was used as the main model for extensive evaluation. About 4% (n = 4) of dose was recovered unchanged in the GI tract after i.v. injection while about 40% (n = 12) was recovered after a 120-fold (0.05-6 mg) dose range of oral administration. In another study 70% of the oral dose eventually disappearing (presumably due to absorption and first-pass elimination) from the GI tract was estimated to occur in just 20 min. These data indicate an unsaturable, incomplete, site-specific absorption as well as a lack of dissolution-rate-limited absorption at the doses studied. Based on plasma data, oral bioavailability in four rats was only 30%, and the HFPE much less than 10%. After oral administration, 61% of the dose was absorbed and/or metabolized in the GI recovery study. Thus, 20-30% of oral dose in rats must be metabolized in the GI wall during absorption. The metabolic activity of stomach (homogenate) ...Continue Reading

References

Dec 1, 1978·European Journal of Clinical Pharmacology·F AndreasenE Mikkelsen
Jul 1, 1979·Clinical Pharmacokinetics·R E Cutler, A D Blair
Feb 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·L Z Benet
Aug 1, 1978·Clinical Pharmacology and Therapeutics·A RaneR A Branch
Jan 1, 1979·Journal of Pharmaceutical Sciences·S Oie, D Jung
Apr 1, 1977·British Journal of Clinical Pharmacology·R A BranchD Levine
Oct 1, 1977·Clinical Pharmacology and Therapeutics·J HonariR E Cutler
Oct 10, 1975·European Journal of Clinical Pharmacology·B BeermannA Rosén
Oct 1, 1974·Clinical Pharmacology and Therapeutics·C M HuangA Quintanilla
Jan 1, 1974·Scottish Medical Journal·W Rupp
Aug 1, 1982·British Journal of Clinical Pharmacology·F AndreasenK Lorentzen
Aug 1, 1982·Kidney International·D C BraterP Chennavasin
Oct 1, 1982·Journal of Pharmaceutical Sciences·E S WallerJ T Doluisio
Dec 1, 1982·Journal of Pharmaceutical Sciences·M L ChenW L Chiou
Oct 1, 1982·Biopharmaceutics & Drug Disposition·M M Hammarlund, L K Paalzow
Nov 1, 1982·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·S InuiS Asada
Oct 1, 1981·Clinical Pharmacology and Therapeutics·R FullerS T Ingalls
Dec 1, 1981·Journal of Pharmacokinetics and Biopharmaceutics·S M HuangW L Chiou

Citations

Apr 6, 2012·Archives of Pharmacal Research·Yu Kyung LeeYoung Hee Choi
Jan 1, 1991·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·F AndreasenE Steiness
Aug 30, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Unji LeeHee E Kang
Feb 1, 1995·Journal of Clinical Pharmacy and Therapeutics·M J KangM G Lee
Nov 1, 1995·British Journal of Pharmacology·J VergésP du Souich
Apr 11, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Paul NkansahJohn Litchfield
Aug 29, 2006·Journal of Pharmaceutical Sciences·Young H ChoiMyung G Lee
Aug 6, 2004·Journal of Pharmaceutical Sciences·Soo K BaeMyung G Lee
Mar 18, 2006·Journal of Pharmaceutical Sciences·Soo K BaeMyung G Lee
May 28, 2005·Journal of Pharmaceutical Sciences·Soo K BaeMyung G Lee
Jan 12, 2010·International Journal of Pharmaceutics·A ZvonarM Gasperlin
Sep 19, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Dae Y LeeMyung G Lee
Oct 16, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Dae Y LeeMyung G Lee
Feb 6, 2007·International Journal of Pharmaceutics·Young H ChoiMyung G Lee
Nov 27, 2004·The Journal of Pharmacy and Pharmacology·Hyun J ShimMyung G Lee
Jul 30, 2009·Biopharmaceutics & Drug Disposition·Young H ChoiMyung G Lee
Jul 11, 2009·Biopharmaceutics & Drug Disposition·Hye J ChungMyung G Lee
May 15, 2004·The Journal of Pharmacy and Pharmacology·Soo Kyung BaeMyung G Lee
Sep 19, 2007·British Journal of Clinical Pharmacology·Laurent HaegeliStephan Krähenbühl
Aug 13, 2008·Biopharmaceutics & Drug Disposition·Si H YangMyung G Lee
Feb 20, 2009·British Journal of Pharmacology·C Y AhnW G Shin

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.