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10.1208/s12248-014-9623-6 http://scihub22266oqcxt.onion/10.1208/s12248-014-9623-6 24912797PopulationPharmacokineticModelingofLY2189102afterMultipleIntravenousandSubcutaneousAdministrations.!4147062!24912797; 2189102     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24912797; 2189102&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 400 Bad Request in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       AAPS+J;+Oncogene 2014 ; 16; 5 (5; 5): 1009-17; 657-61 Nephropedia Template TP {{tp|p=24912797; 2189102|t=2014. Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations ; Transcriptional activation by human c-myb and v-myb genes |pdf=|usr=}}{{24912797; 2189102}} gab.com Text Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations ; Transcriptional activation by human c-myb and v-myb genes JO: AAPS J; Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24912797; 2189102 #FOAvip Interleukin-1 beta (IL-1beta) is an inflammatory mediator which may contribute to the pathophysiology of rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). Population pharmacokinetics (PK) of LY2189102, a high affinity anti-IL-1beta humanized monoclonal immunoglobulin G4 evaluated for efficacy in RA and T2DM, were characterized using data from 79 T2DM subjects (Study H9C-MC-BBDK) who received 13 weekly subcutaneous (SC) doses of LY2189102 (0.6, 18, and 180 mg) and 96 RA subjects (Study H9C-MC-BBDE) who received five weekly intravenous (IV) doses (0.02-2.5 mg/kg). Frequency of anti-drug antibody (ADA) development appears dose-dependent and is different between studies (36.7% in Study H9C-MC-BBDK vs. 2.1% in Study H9C-MC-BBDE), likely due to several factors, including differences in patient population and background medications, administration routes, and assays. A two-compartment model with dose-dependent bioavailability best characterizes LY2189102 PK following IV and SC administration. Typical elimination and distribution clearances, central and peripheral volumes of distribution are 0.222 L/day, 0.518 L/day, 3.08 L, and 1.94 L, resulting in a terminal half-life of 16.8 days. Elimination clearance increased linearly, yet modestly, with baseline creatinine clearance and appears 37.6% higher in subjects who developed ADA. Bioavailability (0.432-0.721) and absorption half-life (94.3-157 h) after SC administration are smaller with larger doses. Overall, LY2189102 PK is consistent with other therapeutic humanized monoclonal antibodies and is likely to support convenient SC dosing.; The human c-myb proto-oncogene is the cellular progenitor of the viral v-myb oncogene and codes for a 75 kD protein involved in growth regulation and differentiation in a number of cells. Fusion proteins in which human c-myb sequences are linked to the DNA binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene which carries the chloramphenicol acetyl transferase (CAT) gene linked in cis to a repeat of the GAL4 binding site. Deletions of carboxyterminal sequences allowed the identification of the domain responsible for transcriptional activation, which is located between amino acid residues 275 to 327. Deletion of this activator domain results in abrogation of the transcriptional activation. The GAL4-v-myb fusion protein can also activate transcription whereas no transactivation by GAL4-c-myb is observed, indicating that a carboxyterminal domain of c-myb which is absent from v-myb apparently negatively regulates transcriptional activation. Dimer formation which is required for transactivation by GAL4 fusion proteins can, when GAL4 is truncated, be mediated by a region of the c-myb protein upstream of the transactivator domain possibly including the transactivator domain itself but not a putative leucine zipper located downstream of this region. Twit Text FOAVip Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations ; Transcriptional activation by human c-myb and v-myb genes ????AAPS J; Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24912797; 2189102 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24912797; 2189102 #FOAvip English Wikipedia <ref>{{Cite pmid|24912797; 2189102}}</ref> Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations ; Transcriptional activation by human c-myb and v-myb genes #MMPMID24912797; 2189102 Bihorel S; Fiedler-Kelly J; Ludwig E; Sloan-Lancaster J; Raddad E; Kalkbrenner F; Guehmann S; Moelling K AAPS J; Oncogene 2014[Sep]; 16; 5 (5; 5): 1009-17; 657-61 PMID24912797; 2189102show ga Interleukin-1 beta (IL-1beta) is an inflammatory mediator which may contribute to the pathophysiology of rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). Population pharmacokinetics (PK) of LY2189102, a high affinity anti-IL-1beta humanized monoclonal immunoglobulin G4 evaluated for efficacy in RA and T2DM, were characterized using data from 79 T2DM subjects (Study H9C-MC-BBDK) who received 13 weekly subcutaneous (SC) doses of LY2189102 (0.6, 18, and 180 mg) and 96 RA subjects (Study H9C-MC-BBDE) who received five weekly intravenous (IV) doses (0.02-2.5 mg/kg). Frequency of anti-drug antibody (ADA) development appears dose-dependent and is different between studies (36.7% in Study H9C-MC-BBDK vs. 2.1% in Study H9C-MC-BBDE), likely due to several factors, including differences in patient population and background medications, administration routes, and assays. A two-compartment model with dose-dependent bioavailability best characterizes LY2189102 PK following IV and SC administration. Typical elimination and distribution clearances, central and peripheral volumes of distribution are 0.222 L/day, 0.518 L/day, 3.08 L, and 1.94 L, resulting in a terminal half-life of 16.8 days. Elimination clearance increased linearly, yet modestly, with baseline creatinine clearance and appears 37.6% higher in subjects who developed ADA. Bioavailability (0.432-0.721) and absorption half-life (94.3-157 h) after SC administration are smaller with larger doses. Overall, LY2189102 PK is consistent with other therapeutic humanized monoclonal antibodies and is likely to support convenient SC dosing.; The human c-myb proto-oncogene is the cellular progenitor of the viral v-myb oncogene and codes for a 75 kD protein involved in growth regulation and differentiation in a number of cells. Fusion proteins in which human c-myb sequences are linked to the DNA binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene which carries the chloramphenicol acetyl transferase (CAT) gene linked in cis to a repeat of the GAL4 binding site. Deletions of carboxyterminal sequences allowed the identification of the domain responsible for transcriptional activation, which is located between amino acid residues 275 to 327. Deletion of this activator domain results in abrogation of the transcriptional activation. The GAL4-v-myb fusion protein can also activate transcription whereas no transactivation by GAL4-c-myb is observed, indicating that a carboxyterminal domain of c-myb which is absent from v-myb apparently negatively regulates transcriptional activation. Dimer formation which is required for transactivation by GAL4 fusion proteins can, when GAL4 is truncated, be mediated by a region of the c-myb protein upstream of the transactivator domain possibly including the transactivator domain itself but not a putative leucine zipper located downstream of this region. |*Models, Biological[MESH] |*Saccharomyces cerevisiae Proteins[MESH] |*Transcription Factors[MESH] |Amino Acid Sequence[MESH] |Anti-Inflammatory Agents/*administration & dosage/blood/*pharmacokinetics[MESH] |Antibodies, Monoclonal, Humanized/*administration & dosage/blood/*pharmacokinetics[MESH] |Arthritis, Rheumatoid/blood/*drug therapy/immunology[MESH] |Biological Availability[MESH] |DNA-Binding Proteins[MESH] |DNA/genetics[MESH] |Diabetes Mellitus, Type 2/blood/*drug therapy/immunology[MESH] |Drug Administration Schedule[MESH] |Drug Dosage Calculations[MESH] |Fungal Proteins/genetics[MESH] |Genes, Regulator/physiology[MESH] |Half-Life[MESH] |Humans[MESH] |Hypoglycemic Agents/*administration & dosage/blood/*pharmacokinetics[MESH] |Injections, Intravenous[MESH] |Injections, Subcutaneous[MESH] |Linear Models[MESH] |Metabolic Clearance Rate[MESH] |Molecular Sequence Data[MESH] |Oncogene Proteins v-myb[MESH] |Proto-Oncogene Mas[MESH] |Proto-Oncogene Proteins c-myb[MESH] |Proto-Oncogene Proteins/*genetics/physiology[MESH] |Randomized Controlled Trials as Topic[MESH] |Retroviridae Proteins, Oncogenic/*genetics/physiology[MESH] |Trans-Activators/physiology[MESH] |Transcription, Genetic/*drug effects[MESH]Population pharmacokinetic modeling of LY2189102 after multiple intrav(epmc).pdf DeepDyve Pubget Overpricing