scholarly journals A Screen of Approved Drugs Identifies the Androgen Receptor Antagonist Flutamide and Its Pharmacologically Active Metabolite 2-Hydroxy-Flutamide as Heterotropic Activators of Cytochrome P450 3A In Vitro and In Vivo

2015 ◽  
Vol 43 (11) ◽  
pp. 1718-1726 ◽  
Author(s):  
Anna L. Blobaum ◽  
Frank W. Byers ◽  
Thomas M. Bridges ◽  
Charles W. Locuson ◽  
P. Jeffrey Conn ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Androgen Receptor ◽  
Receptor Antagonist ◽  
Active Metabolite ◽  
Cytochrome P450 3A ◽  
Androgen Receptor Antagonist ◽  
Approved Drugs ◽  
Pharmacologically Active

The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro

1999 ◽  
Vol 15 (1-2) ◽  
pp. 80-93 ◽  
Author(s):  
Joseph Ostby ◽  
William R. Kelce ◽  
Christy Lambright ◽  
Cynthia J. Wolf ◽  
Peter Mann ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Antagonist ◽  
Sexual Differentiation ◽  
Male Rat ◽  
Androgen Receptor Antagonist

Does Crizotinib Auto-Inhibit CYP3A in vivo?

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 715-718
Author(s):  
Abigail R. Bland ◽  
Nensi Shrestha ◽  
Rhonda J. Rosengren ◽  
John C. Ashton
Keyword(s):  
Lung Cancer ◽  
Cytochrome P450 ◽  
Western Blot ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitor ◽  
Cyp3a Activity ◽  
Cytochrome P450 3A ◽  
Anaplastic Lymphoma

Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin <i>N</i>-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.

scholarly journals Inhibitory Effect of Lygodium Root on the Cytochrome P450 3A Enzyme in vitro and in vivo

2020 ◽  
Vol Volume 14 ◽  
pp. 1909-1919
Author(s):  
Yunfang Zhou ◽  
Ailian Hua ◽  
Quan Zhou ◽  
Peiwu Geng ◽  
Feifei Chen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
Cytochrome P450 3A

scholarly journals The Mechanism of Action of Cyclophosphamide and Its Consequences for the Development of a New Generation of Oxazaphosphorine Cytostatics

2020 ◽  
Vol 88 (4) ◽  
pp. 42
Author(s):  
Georg Voelcker
Keyword(s):  
Mechanism Of Action ◽  
Active Metabolite ◽  
Dna Alkylation ◽  
In Vivo Metabolism ◽  
Pharmacologically Active ◽  
New Generation ◽  
Anti Tumor Activity ◽  
Oxazaphosphorine Cytostatics

Although cyclophosphamide (CP) has been used successfully in the clinic for over 50 years, it has so far not been possible to elucidate the mechanism of action and to use it for improvement. This was not possible because the basis of the mechanism of action of CP, which was found by lucky coincidence, is apoptosis, the discovery of which was honored with the Nobel Prize only in 2002. Another reason was that results from cell culture experiments were used to elucidate the mechanism of action, ignoring the fact that in vivo metabolism differs from in vitro conditions. In vitro, toxic acrolein is formed during the formation of the cytotoxic metabolite phosphoreamidemustard (PAM), whereas in vivo proapoptotic hydroxypropanal (HPA) is formed. The CP metabolites formed in sequence 4-hydroxycyclophosphamide (OHCP) are the main cause of toxicity, aldophosphamide (ALDO) is the pharmacologically active metabolite and HPA amplifies the cytotoxic apoptosis initiated by DNA alkylation by PAM. It is shown that toxicity is drastically reduced but anti-tumor activity strongly increased by the formation of ALDO bypassing OHCP. Furthermore, it is shown that the anti-tumor activity against advanced solid P388 tumors that grow on CD2F1 mice is increased by orders of magnitude if DNA damage caused by a modified PAM is poorly repairable.

scholarly journals In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

2017 ◽  
Vol 10 (6) ◽  
pp. 576-581 ◽  
Author(s):  
Sunday O. Nduka ◽  
Mathew J. Okonta ◽  
Daniel L. Ajaghaku ◽  
Chinwe V. Ukwe
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Inhibition ◽  
Cytochrome P450 3A

scholarly journals Interaction Between Florfenicol and Doxycycline Involving Cytochrome P450 3A in Goats (Capra hricus)

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaojing Wang ◽  
Yaqin Yang ◽  
María-Aránzazu Martínez ◽  
Marta Martínez ◽  
Bernardo Lopez-Torres ◽  
...  
Keyword(s):  
Health Hazard ◽  
Liver Microsomes ◽  
Quantitative Prediction ◽  
Withdrawal Period ◽  
Cytochrome P450 3A ◽  
Key Enzyme ◽  
Liver And Kidney ◽  
Pharmacologically Active

When two drugs are combined, drug-drug interactions (DDI) often occur. Metabolic DDI usually occur due to inhibition of the metabolism of one drug by the other. This leads to an increase in the plasma concentration of the drug whose metabolism is inhibited. The objective of this research study was to verify the DDI risk of two antibacterial, florfenicol (FF) and doxycycline (DOX) due to metabolism. Because food containing residues of any pharmacologically active substance could potentially constitute a public health hazard, we selected a food producing animal, goat, goat liver microsomes and recombinant metabolic enzymes, for in vivo and in vitro metabolism studies. In vitro experiments showed that CYP3A was the key enzyme subfamily in FF metabolism, DOX slowed down FF metabolism and R440 was possibly the key amino acid in the metabolic interaction between FF and DOX. In vivo studies in the goats showed that DOX inhibited up-regulation of CYP3A24 gene expression produced by FF; in liver and kidney, DOX slightly slowed down FF metabolism. Quantitative prediction of DDI risk suggest that when DOX is used in combination with FF in veterinary medicine, may result in a clinical significant increase of FF plasma and tissue concentrations, resulting a prevalence of harmful tissue residues of medicinal products in the food chain. Through our experimentation, when DOX is used in combination with FF, the withdrawal period of FF in the kidney was extended by 1 day. Otherwise, an appropriate withdrawal period (20 days) of FF was established for FF and DOX combined use to ensure that the animal can be safely slaughtered for food.

Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations

2013 ◽  
Vol 52 (5) ◽  
pp. 333-345 ◽  
Author(s):  
Ibrahim Ince ◽  
Catherijne A. J. Knibbe ◽  
Meindert Danhof ◽  
Saskia N. de Wildt
Keyword(s):  
Cytochrome P450 ◽  
Developmental Changes ◽  
Cytochrome P450 3A ◽  
And Function
Sign in / Sign up

Export Citation Format

Share Document