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Microsoft word - tables greim15-7-2006.doc
Phase I and phase II are metabolic processes. Hydrophilic compound do
not need metabolism to be excreted.
Phase I, Phase II and Phase III enzymes Phase-I-Enzymes
Monoamine oxidases (MAO) Cyclooxygenases (COX)
DT-Diaphorases (NQOR) Alcohol dehydrogenases (ADH)
Transferases Glutathiontransferases (GST)
Sulfotransferases (SULT) Acetyltransferases (NAT)
Transporters Organic anion-transporting polypeptides (OATP)
ATP Binding Cassette transporter family B1 (ABCB1)1
ATP Binding Cassette transporter family C1 (ABCC1)2
2 Multidrug resistance-associated proteins (MRP)
Changes of lipophilicty of compounds by metabolism. Phase II is more
efficient in changing lipophilicity than phase I.
1octanol/water partition coefficient. Logarithm of partition coefficient, P=[Organic] / [Aqueous]. Octanol models body fat, water models body water
. Human and mouse putuative ful -length CYP genes. Currently 57 Human
CYP genes are known (and 58 pseudogenes). This number is expected to be
complete. Each gene additional y has its al elic variants.
B Subfamilies in mice with only pseudogene orthologs in humans The gene names are listed numerical y and alphabetical y by subfamilies, and pairing does not necessarily denote orthologous genes, e.g. it is not known whether human CYP2A6 is the ortholog of mouse Cyp2a4. Genes having the identical combination of numbers and letters are orthologs between the two species (adapted from Nelson et al. Pharmacogenetics, 2004).
. In vivo substrates for cytochrome P450 enzymes.
Remark: CYP1A1 is only present after induction
. Quantitation of and quantitative role in xenobiotica metabolism of
cytochrome P450 isoenzymes. Amount of cytochrome P450 in liver was determined
by immunoquantitation. Participation of cytochrome P450 enzymes in metabolism of
drugs is estimated. CYP2D6 is overrepresented in drug metabolism.
Functional polymorphisms of cytochrome P450 enzymes CYP enzyme
Most frequent genotype to
yield poor metabolism
Polymorphism of cytochromes P450 with clinical relevance and their probe
substrate. Almost al phase I enzymes exhibit genomic polymorphisms. Most phase I
enzymes exhibit clinical y relevant genetic polymorphisms. However, the
polymophisms listed below are general y accepted and more frequently encountered. Cytochrome1 Phenotype
ß-blockers, i.e. propafenone Antidepressants, i.e imipramine
1 for more polymorphisms see http://www.sciencemag.org/feature/data/1044449.dtl
and http://www.imm.ki.se/CYPal eles/, accessed January 2006
3 for more substrates see http://www.sciencemag.org/feature/data/1044449.dtl and
http://www.pharmgkb.org, accessed january 2006
Subdivision of esterases as subfamilies of α, ß-hydrolases
TiLLiT Español La dama boba Personajes LISEO, caballero – Gianluca Poma TURIN, lacayo - Erika Mancin OTAVIA, madre – Federica Sali MISENA, su amiga y Duardo – Romina Hoxha LAURENCIO, caballero - Federico Riesi MAESTROS – Gerta Delia NISE, dama – Mary Cartia FINEA, su hermana – Desirè Massarenti CLARA, criada – Luna Pozzati CELIA,
FCR versus BR in first line therapy of CLL 1. PROTOCOL SYNOPSIS CLL10 protocol of the German CLL-Study Group (GCLLSG) Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) alone in patients with previously untreated chronic lymphocytic leukaemia Representative and Coordinating Principal Al