Interaction profiling

Due to the short period of clinical use, the interaction profile of COX-2-selective inhibitors cannot be entirely described at the present time. 

Differentiate antidepressants according to pharmacologic properties, adverse-effect profiles, pharmacokinetic profiles, drug interaction profiles, and dosing features. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

Haab BB Advances in protein microarray technology for protein expression and interaction profiling. Curr Opin Drug Discovery Dev 2001 4 116-123. 

In the general case, when arbitrary interaction profiles prevail, the particle deposition rate must be obtained by solving the complete transport equations. The first numerical solution of the complete convective diffusional transport equations, including London-van der Waals attraction, gravity, Brownian diffusion and the complete hydrodynamical interactions, was obtained for a spherical collector [89]. Soon after, numerical solutions were obtained for a panoplea of other collector geometries... 

Fig. 9.3. Several mechanisms underlie the functional versatility of the ER. The different distributions of the alpha and beta isotypes of ER conditions a first step that warrants distinct functional profiles depending on the higher or lower affinity of the ligand for one or another isotype (upper panel). Then, differentligands generate distinct 3D conformations in the ligand-receptor complex that condition different interaction profiles with the promoters of target genes (lower panel)...

Today s pharmaceuticals are not the routine antibiotics of yesteryear. FDA is now approving more sophisticated and complicated chemical entities with complex risk/benefit profiles. Some products currently on the market, such as Accutane (isotretinoin, Hoffmann-LaRoche, Nutley NJ, U.S.A.), might not be there without patient information accompanying the product. Patients must understand the risks and limitations of medical products so they can use them properly. By necessity, patient education will become more critical as regulatory agencies approve more drugs with complicated regimens and interaction profiles. 

Pearce KH, larmone MA, Simmons CA, et al. Discovery of novel nuclear receptor modulating ligands an integral role for peptide interaction profiling. Drug Discov Today 2004 9 741-51. 

Oxcarbazepine is a derivative of carbamazepine and although its precise mechanism of action is unknown it has similar properties as carbamazepine and is also used for the treatment of primary generalized tonic-clonic seizures and partial seizures. Also the adverse effects are similar to those of carbamazepine. However the drug interaction profile is different as oxcarbazepine has hardly any enzyme-inducing capacity. 

Acceptable drug metabolism and interaction profiles based on microsomal and recombinantly expressed cytochrome P450 isoenzyme studies Recent addition Toxicogenomic data for early assessment of alteration in expression of RNA transcripts (and therefore proteins) related to toxic responses so that modification of safer and more potent variants of NME could be made and identified early... 

Rifapentine is an analog of rifampin. It is active against both M tuberculosis and Mavium. As with all rifamycins, it is a bacterial RNA polymerase inhibitor, and cross-resistance between rifampin and rifapentine is complete. Like rifampin, rifapentine is a potent inducer of cytochrome P450 enzymes, and it has the same drug interaction profile. Toxicity is similar to that of rifampin. Rifapentine and its microbiologically active metabolite, 25-desacetylrifapentine, have an elimination half-life of 13 hours. Rifapentine is indicated for treatment of tuberculosis caused by rifampin-susceptible strains. The dose is 600 mg once or twice weekly. Whether rifapentine is as effective as rifampin has not been established, and rifampin therefore remains the rifamycin of choice for treatment of tuberculosis. 

Chuaqui, C., Deng, Z., Singh, J., Interaction profiles of protein kinase-inhibitor complexes and their application to virtual screening. I. Med. Chem. 2005, 48, 121-133. 

This chapter has introduced interaction profiling as a new and powerful approach to understand what interactions small molecules exploit in order to be competitive against ATP and, often, selective for a particular kinase. More importantly, we have shown that the information encoded in the interaction pro-... 

Farha MA, Brown ED (2010) Chemical probes of Escherichia coli uncovered through chemical-chemical interaction profiling with compounds of known biological activity. Chem Biol 17 852-862... 

Figure 2, Solvent interactive profiles (the three bottom scales show the interactive strengths of the solvents hydrogen donor, hydrogen acceptor, and dipole)...

When the Bom, double-layer, and van der Waals forces act over distances that are short compared to the diffusion boundary-layer thickness, and when the e forces form an energy hairier, the adsorption and desorption rates may be calculated by lumping the effect of the interactions into a boundary condition on the usual ccm-vective-diffusion equation. This condition takes the form of a first-order, reversible reaction on the collector s surface. The apparent rate constants and equilibrium collector capacity are explicitly related to the interaction profile and are shown to have the Arrhenius form. They do not depend on the collector geometry or flow pattern. 

Figures 1 to 3 illustrate die quantitative effect of various properties on the interaction profile (it). Four observations are noteworthy. First, diere exists a narrow range of Hamaker s constant and surface potentials for which a maximum = (hmax) ] and two minima...

This corresponds to mass-transfer limitation of the apparent surface reaction. Thus the combination of Eqs. p] and 2] is expected to give reasonable estimates of the rate of deposition for all particle-collector interaction profiles, provided the interactions are confined to a region which is thin compared to the diffusion boundary layer. 

Figure 3. Particle-polymer brushed surface interaction profile, (a) particle-surface contact (b) dispersion interaction (c) electrical double layer interaction osmotic polymer-brush particle interaction.

The suprahypothalamic neurotransmitter level can be assessed by a determination of catecholamines in circumscribed brain areas, the technique requires preparation of frozen tissue and isolation of specific nuclei by the micropunch technique. The catecholamines and indolamines can be measured by a radio-enzymatic methods and by a high-pressure liquid chromatography (HPLC) with electrochemical detection. These mechanistic investigations are mostly initiated due to questions arising from the receptor interaction profile of the drug candidate, they may be required to prove that such receptor interactions truly change the functional state of neurotransmitters (functional expression). Mostly, however, the peripheral effects of such neurotransmitter mechanisms (for instance prolactin secretion) are sufficiently distinct. 

ATSDR. 2004a. Guidance manual for the assessment of joint toxic action of chemical mixtures. Agency for Toxic Substances and Disease Registry. Atlanta (GA) US Department of Health and Human Services. Available from http //www.atsdr.cdc.gov/interaction-profiles/ipga.html... 

Pohl HR, Roney N, Wilbur S, Hansen H, De Rosa CT, 2003. Six interaction profiles for simple mixtures. Chemosphere 53 183-197. 

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