Biomaterial Database

Metabolism of ketotifen by human liver microsomes. In vitro characterization of a tertiary amine glucuronidation. 1983

J F Le Bigot, and T Cresteil, and J R Kiechel, and P Beaune

Biotransformation of ketotifen was investigated in vitro using human liver microsomes. Three of the four metabolic pathways observed in vivo in man were exhibited under the conditions of incubation, namely demethylation, N-oxidation, and N-glucuronidation, the absent route being the ketoreduction, which probably has a cytosolic localization. The kinetic parameters of the N-glucuronidation (KM for ketotifen and UDPGA and Vmax) were determined with native and detergent-treated microsomes. Treatment by Triton X-100 increased by about 3-fold the conjugation reaction. No sex difference was observed and N-glucuronidation did not seem to be inhibited either by bilirubin or by 4-nitrophenol. Thus, human liver microsomes are a useful and suitable in vitro model for studying metabolic routes, specific for man, as in the case of ketotifen. Obviously, the results obtained can only reflect partially the multiplicity of in vivo events and interpretation has to be complemented by investigations with other models.

UI	MeSH Term	Description	Entries
D007665	Ketotifen	A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.	4,9-Dihydro-4-(1-methyl-4-piperidylidene)-10H-benzo(4,5)-cyclohepta(1,2-b)thiophen-10-one,Ketotifen Fumarate,Ketotifene,Ketotiphen,Ketotiphene,Zaditen,Fumarate, Ketotifen
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009596	Nitrophenols	PHENOLS carrying nitro group substituents.	Nitrophenol
D005965	Glucuronates	Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.	Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D001663	Bilirubin	A bile pigment that is a degradation product of HEME.	Bilirubin IX alpha,Bilirubin, (15E)-Isomer,Bilirubin, (4E)-Isomer,Bilirubin, (4E,15E)-Isomer,Bilirubin, Calcium Salt,Bilirubin, Disodium Salt,Bilirubin, Monosodium Salt,Calcium Bilirubinate,Hematoidin,delta-Bilirubin,Bilirubinate, Calcium,Calcium Salt Bilirubin,Disodium Salt Bilirubin,Monosodium Salt Bilirubin,Salt Bilirubin, Calcium,delta Bilirubin
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In