Table 1. Phase I and phase II are metabolic processes. Hydrophilic compound do not need metabolism to be excreted. Hydrophilic Lipophilic compound compound Table 2. Phase I, Phase II and Phase III enzymes Phase-I-Enzymes
Monoamine oxidases (MAO) Cyclooxygenases (COX)
DT-Diaphorases (NQOR) Alcohol dehydrogenases (ADH)
Phase-II-Enzymes:
Transferases Glutathiontransferases (GST)
Sulfotransferases (SULT) Acetyltransferases (NAT)
Phase III-Enzymes:
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)
Table 3. Changes of lipophilicty of compounds by metabolism. Phase II is more efficient in changing lipophilicity than phase I. Compound Metabolite
1octanol/water partition coefficient. Logarithm of partition coefficient, P=[Organic] / [Aqueous]. Octanol models body fat, water models body water
Table 4. 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).
Table 5. In vivo substrates for cytochrome P450 enzymes. Marker substrate Marker substrate
Remark: CYP1A1 is only present after induction
Table 6. 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.
Table 7. Functional polymorphisms of cytochrome P450 enzymes CYP enzyme Wild-type allele Most frequent genotype to yield poor metabolism Table 8. 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 Substrate3 In-vivo probe4 with mutation
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
Table 9. Subdivision of esterases as subfamilies of α, ß-hydrolases Subfamily Abbreviation Substrate
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