Evaluation of the assumptions of an ontogeny model of rat hepatic cytochrome P450 activity

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Jane AlcornPatrick J McNamara


We previously reported an ontogeny model of hepatic cytochrome P450 (P450) activity that predicts in vivo P450 elimination from in vitro intrinsic clearance. The purpose of this study was to conduct investigations into key assumptions of the P450 ontogeny model using the developing rat model system. We used two developmentally dissimilar enzymes, CYP2E1 and CYP1A2, and male rats (n = 4) at age groups representing critical developmental stages. Total body and liver weights and hepatic microsomal protein contents were measured. Following high-performance liquid chromatography analysis, apparent K(M) and V(max) estimates were calculated using nonlinear regression analysis for CYP2E1- and CYP1A2-mediated chlorzoxazone 6-hydroxylation and methoxyresorufin O-dealkylation, and V(max) estimates for p-nitrophenol and phenacetin hydroxylations, respectively. Hepatic scaling factors and V(max) values provided estimates for infant scaling factors (ISF). The data show microsomal protein contents increased with postnatal age and reached adult values after postnatal day (PD) 7. Apparent K(M) values were similar at all developmental stages except at < or =PD7. Developmental increases in probe substrate V(max) values did not correlate with the ...Continue Reading


Sep 1, 1987·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·T Cresteil
Nov 1, 1993·The International Journal of Biochemistry·J T BorlakogluC R Wolf
May 1, 1993·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·F JahnW Klinger
Jul 17, 1996·Toxicology·L J Graeter, M E Mortensen
Dec 31, 1997·Microscopy Research and Technique·K J Rich, A R Boobis
Jan 9, 1998·Drug Metabolism Reviews·J B Houston, D J Carlile
Sep 12, 2002·Clinical Pharmacokinetics·Jane Alcorn, Patrick J McNamara
Oct 31, 2002·Clinical Pharmacokinetics·Jane Alcorn, Patrick J McNamara
Mar 7, 2003·Clinical Pharmacology and Therapeutics·Gideon KorenGerrard Pons
Mar 19, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anthony Y H LuJiunn H Lin
Feb 3, 2004·Environmental Health Perspectives·Gary GinsbergBabasaheb Sonawane
Oct 27, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Robert L Brent
Jan 22, 2005·Risk Analysis : an Official Publication of the Society for Risk Analysis·Leona H ClarkHugh A Barton
Jul 16, 2005·Inhalation Toxicology·Annie M JarabekFrederick J Miller
Jul 16, 2005·Journal of Toxicology and Environmental Health. Part a·Hugh A Barton
Oct 27, 2005·Current Drug Metabolism·Wei TangAnthony Y H Lu
Dec 6, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sathanandam S AnandJames V Bruckner
Feb 25, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Fawzy A ElbarbryJane Alcorn
Jun 29, 2006·Clinical Pharmacokinetics·Andrea N EdgintonStefan Willmann
Aug 25, 2006·Clinical Pharmacokinetics·Trevor N JohnsonGeoffrey T Tucker
Mar 17, 2007·Journal of Biochemical and Molecular Toxicology·Fawzy A ElbarbryJane Alcorn


Mar 18, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rebecca A ClewellSusan J Borghoff
Mar 22, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lai PengXiao-Bo Zhong
Sep 25, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ravi Shankar Prasad SinghJane Alcorn
Nov 21, 2013·British Journal of Clinical Pharmacology·Jeffrey S Barrett
Apr 20, 2012·Critical Reviews in Toxicology·Shakil Ahmed SaghirAlene Theresa McCoy
Apr 14, 2009·Research in Veterinary Science·Fawzy A Elbarbry, Jane Alcorn
Nov 10, 2013·Regulatory Toxicology and Pharmacology : RTP·Jordan Ned SmithTorka S Poet
Jul 9, 2016·Chemico-biological Interactions·Brooks T McPhailJames V Bruckner
Jun 14, 2008·Drug Discovery Today·Jane Alcorn, Patrick J McNamara
Apr 28, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jordan Ned SmithTorka S Poet
Aug 24, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dan LiCheng Guo
Jul 17, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Laura HedgesBrian G Lake
Sep 12, 2017·Journal of Toxicology and Environmental Health. Part a·Gary GinsbergBabasaheb Sonawane

Related Concepts

Trending Feeds


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.