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Elimination Process (elimination + process)
Selected AbstractsPharmacokinetic aspects of biotechnology productsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Lisa Tang Abstract In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. The first challenge frequently comes from a lack of sophistication in various analytical techniques for the quantification of peptide and protein drugs in biological matrices. However, advancements in bioassays and immunoassays,along with a newer generation of mass spectrometry-based techniques,can often provide capabilities for both efficient and reliable detection. Selection of the most appropriate route of administration for biotech drugs requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes. Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure to exert the intended pharmacological response. This poses a potential problem, especially for large protein drugs, with their typically limited distribution space. Binding phenomena and receptor-mediated cellular uptake may further complicate this issue. Elimination processes,a critical determinant for the drug's systemic exposure,may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has in the past been identified as a crucial factor for the success of a scientifically driven, evidence-based, and thus accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2184,2204, 2004 [source] Effect of petrochemical sludge concentrations on microbial communities during soil bioremediationFEMS MICROBIOLOGY ECOLOGY, Issue 2 2005María T. del Panno Abstract Qualitative and quantitative changes of microbial communities in soil microcosms during bioremediation were determined throughout one year. The soil was contaminated with 0%, 2.5%, 5%, 10% (wt/wt) of petrochemical sludge containing polynuclear aromatic hydrocarbons. We analyzed the hydrocarbon concentration in the microcosms, the number of cultivable bacteria using CFU and most probable number assays, the community structure using denaturing gradient gel electrophoresis, and the metabolic activity of soil using dehydrogenase activity and substrate-induced respiration assays. After one year of treatment, the chemical analysis suggested that the hydrocarbon elimination process was over. The biological analysis, however, showed that the contaminated microcosms suffered under long-term disturbance. The number of heterotrophic bacteria that increased after sludge addition (up to 108,109 cells ml,1) has not returned to the level of the control soil (2,6 × 107 cells ml,1). The community structure in the contaminated soils differed considerably from that in the control. The substrate-induced respiration of the contaminated soils was significantly lower (,10-fold) and the dehydrogenase activity was significantly higher (20,40-fold) compared to the control. Changes in the community structure of soils depended on the amount of added sludge. The species, which were predominant in the sludge community, could not be detected in the contaminated soils. [source] Mechanism and structure,reactivity correlation in the homogeneous, unimolecular elimination kinetics of 2-substituted ethyl methylcarbonates in the gas phaseJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2003Gabriel Chuchani Abstract The gas-phase elimination kinetics of 2-substituted ethyl methylcarbonates were determined in a static reaction system over the temperature range of 323,435°C and pressure range 28.5,242 Torr. The reactions are homogeneous, unimolecular and follow a first-order rate law. The kinetic and thermodynamic parameters are reported. The 2-substituents of the ethyl methylcarbonate (CH3OCOOCH2CH2Z, Z=substituent) give an approximate linear correlation when using the Taft,Topsom method, log(kZ/kH)=,(0.57±0.19),,+(1.34±0.49),R, (r=0.9256; SD=0.16) at 400°C. This result implies the elimination process to be sensitive to steric factors, while the electronic effect is unimportant. However, the resonance factor has the greatest influence for a favorable abstraction of the ,-hydrogen of the C,,H bond by the oxygen carbonyl. Because ,, is significant, a good correlation of the alkyl substituents of carbonates with Hancock's steric parameters was obtained: log(kR/kH) versus ESC for CH3OCOOCH2CH2R at 400°C, R=alkyl, ,=,0.17 (r=0.9993, SD=0.01). An approximate straight line was obtained on plotting these data with the reported Hancock's correlation of 2-alkyl ethylacetates. This result leads to evidence for the ,-hydrogen abstraction by the oxygen carbonyl and not by the alkoxy oxygen at the opposite side of the carbonate. The carbonate decompostion is best described in terms of a concerted six-membered cyclic transition state type of mechanism. Copyright © 2003 John Wiley & Sons, Ltd. [source] Solvolyses of naphthoyl chlorides.JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2002Grunwald, Solvent effect, Winstein correlation analyses with YxBnCl scales Abstract The solvolyses of 1-naphthoyl (2), 2-naphthoyl (3), 4-methyl-1-naphthoyl (4) and 6-methoxy-2-naphthoyl (5) chlorides in a variety of solvents were studied, and correlation analyses by using the single- and dual-parameter Grunwald,Winstein equations were examined. An excellent linear relationship (R,=,0.995) for 4, log (k/k0),=,0.733YxBnCl,+,0.269NOTs, was observed. An SN1-like mechanism with decreasing extent of nucleophilic solvent participation was found in the solvolysis of 2 and 4. 2-Naphthoyl chloride is likely to have a mechanism at the borderline of SN1-like dissociation and an addition,elimination process. 6-Methoxy-2-naphthoyl chloride shows more SN1-like character than 3 and is associated with nucleophilic solvent intervention more pronounced than that for 2 and 4. The applicability and the advantages of using the YxBnCl scale for different types of substrates are discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] The mechanisms of the homogeneous, unimolecular, elimination kinetics of several , -substituted diethyl acetals in the gas-phaseJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 9 2010José R. Mora Abstract The rates of gas-phase elimination of several , -substituted diethyl acetals have been determined in a static system and seasoned with allyl bromide. The reactions, inhibited with toluene, are homogeneous, unimolecular, and follow first-order law kinetics. These elimination processes involve two parallel reactions. The first parallel reaction yields ethanol and the corresponding ethyl vinyl ether. The latter product is an unstable intermediate and further decomposes to ethylene and the corresponding substituted aldehyde. The second parallel reaction gives ethane and the corresponding ethyl ester. The kinetics has been measured over the temperature range of 370,441,°C and pressure range of 23,160,torr. The rate coefficients are given by the following Arrhenius equations: The differences in the rates of ethanol formation may be attributed to electronic transmission of the , -substituent. The comparative kinetic and thermodynamic parameters of the parallel reactions suggest two different concerted polar four-membered cyclic transition state types of mechanisms. Copyright © 2010 John Wiley & Sons, Ltd. [source] | ||||||||||