Metabolic interactions

Drug interactions Metabolized by CYP450 3A4 (e.g., cyclosporine, erythromycin, itraconazole, phenytoin, St. John s wort)... 

Drugs that cause induction or inhibition of enzymes may affect the metabolism of concomitantly administered drugs, as well as of hormones and other endogenous substances. For this reason, such properties are considered undesirable, and sometimes they might constitute sufficient reason to discontinue drug development. At the very least, studies will be required to assess the magnitude of effect of likely interactions. Metabolic and toxicity studies in animals will... 

Ito K, Iwatsubo T, Kanamitsu S, et al. Prediction of pharmacokinetic alterations caused by drug-drug interactions metabolic interaction in the liver. Pharmacol Rev 1998 50 387-412. 

Target Information database - The Database contains information such as Protein-Protein interactions, Metabolic and Signaling Pathways, Transcription factors, post-Translational modifications, Disease information, various Drugs and Clinical compounds and the Companies of interest. 

H. M. Sauro. Jarnac a system for interactive metabolic analysis. In J.-H. Hofmeyr, J. M. Rohwer, and J. Snoep, editors, Animating the Cellular Map. 9th International BioThermoKinetics Meeting, chapter 33, pages 221-228. Stellenbosch University Press, Stellenbosch, 2000. 

In vitro target specificity CeU-free assays CeU assays Protein binding Drug-drug interaction Metabolic stability CeU-based toxicity Membrane permeability... 

Macrolides are metabolized primarily in the liver with their metabolites excreted into bile metabolism occurs to a lesser degree in the kidneys and lungs [259, 260]. Since macrolides vary widely in their serum and tissue concentrations, half-lives, and active metabolites, knowledge of their metabolism is important for optimizing dosage schedules. Some macrolides also influence the metabolism of certain other drugs, and modified metabolic conditions such as liver disease may alter antibiotic concentrations [260-264]. Because such events can lead to toxicity from either excess antibiotic or adverse drug interactions, metabolism is examined in patients... 

Susceptibility factors genetic (long QT syndrome) altered physiology (hypokalemia) drug interactions (metabolism inhibitors drugs that prolong the QT interval) diseases (liver disease cardiac disease with prolongation of QT interval)... 

Drug interactions metabolized by CYP450 3A4, may interact with drugs that inhibit or induce this enzyme May cause hypoglycemia in patients receiving insulin, sulfonylureas, or metformin contraindicated in pregnant women Limit vitamin A supplements... 

In the context of drug-like substances, hydrophobicity is related to absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism and toxicity. Closely related to log P is the octanol-water distribution coefficient (logDpn), accounting for partition of pH-dependent mixture of ionizable species. Ionization of any compound makes it more water soluble and then less lipophilic. The log D can be calculated from log Pand acid dissociation constant pJC, by the following expression [Cronin, Aptula et al, 2002b Livingstone, 2003] ... 

Hydrogen-bond surrogate approach Activation of apoptosis by inhibition of Bcl-xL/Bak interaction Metabolically stable peptides [88]... 

Ito, K, Iwatsubo, T., Kanamitsu, S., Ueda, K, Suzuki, H., Sugiyama, Y (1998). Prediction of Pharmacokinetic Alterations Caused by Drug-Drug Interactions Metabolic Interaction in the Liver. Pharmacologial Reviews, 50, 387—412. 

The expanding availability of information on genetic sequences, polymoiphisms, SNPs, protein variations and interactions, metabolic and phenotypical variants as well as the sensor technologies plus micro- and nanotechnologies in combination with the communication network spanning the globe will allow increasingly precise measurements of the ... 

Tsoka, S., and Ouzounis, C. A. (2000). Prediction of protein interactions Metabolic enzymes are frequently involved in gene fusion. Nat. Genet. 26(2), 141-142. 

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