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10.1111/bcp.12378 http://scihub22266oqcxt.onion/10.1111/bcp.12378 C4243905!4243905 !24617631     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24617631 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Clin+Pharmacol 2014 ; 78 (3 ): 543-55 Nephropedia Template TP {{tp|p=24617631 |t=2014. Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies |pdf=|usr=}}{{24617631 }} gab.com Text Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies JO: Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24617631 #FOAvip AIMS: The aim was to characterize the population pharmacokinetics of BYL719 in cancer patients and assess the time course of tumour response in relation to drug exposure and dosing schedule. METHODS: Plasma samples and longitudinal tumour size measurements were collected from 60 patients with advanced solid malignancies who received oral BYL719 once daily (30-450?mg) or twice daily at 120?mg or 200?mg. Non-linear mixed effect modelling was employed to develop the population pharmacokinetic and pharmacodynamic model. RESULTS: The pharmacokinetics were best described by a one compartment disposition model and transit compartments accounting for the lag time in absorption. The typical population oral clearance and volume of distribution estimates with their between-subject variability (BSV) were 10?l?h(-1) (BSV 26%) and 108?l (BSV 28%), respectively. The estimated optimal number of transit compartments was 8.1, with a mean transit time to the absorption compartment of 1.28?h (BSV 32%). The between-occasion variability in the rate and extent of absorption was 46% and 26%, respectively. Tumour growth was modelled using a turnover model characterized by a zero order growth rate of 0.581?cm?week(1) and a first order death rate of 0.0123 week(-1) . BYL719 inhibited tumour growth with an IC50 of 100?ng?ml(-1) (BSV 154%). Model-based predictions showed potential for additional anti-tumour activity of twice daily dosing at total daily dose below 400?mg, but a loss of efficacy if administered less frequently than once daily. CONCLUSIONS: The proposed model provides a valuable approach for planning future clinical studies and for designing optimized dosing regimens with BYL719. Twit Text FOAVip Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies ????Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24617631 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24617631 #FOAvip English Wikipedia <ref>{{Cite pmid|24617631 }}</ref> Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies #MMPMID24617631 De Buck SS ; Jakab A ; Boehm M ; Bootle D ; Juric D ; Quadt C ; Goggin TK Br J Clin Pharmacol 2014[Sep]; 78 (3 ): 543-55 PMID24617631 show ga AIMS: The aim was to characterize the population pharmacokinetics of BYL719 in cancer patients and assess the time course of tumour response in relation to drug exposure and dosing schedule. METHODS: Plasma samples and longitudinal tumour size measurements were collected from 60 patients with advanced solid malignancies who received oral BYL719 once daily (30-450?mg) or twice daily at 120?mg or 200?mg. Non-linear mixed effect modelling was employed to develop the population pharmacokinetic and pharmacodynamic model. RESULTS: The pharmacokinetics were best described by a one compartment disposition model and transit compartments accounting for the lag time in absorption. The typical population oral clearance and volume of distribution estimates with their between-subject variability (BSV) were 10?l?h(-1) (BSV 26%) and 108?l (BSV 28%), respectively. The estimated optimal number of transit compartments was 8.1, with a mean transit time to the absorption compartment of 1.28?h (BSV 32%). The between-occasion variability in the rate and extent of absorption was 46% and 26%, respectively. Tumour growth was modelled using a turnover model characterized by a zero order growth rate of 0.581?cm?week(1) and a first order death rate of 0.0123 week(-1) . BYL719 inhibited tumour growth with an IC50 of 100?ng?ml(-1) (BSV 154%). Model-based predictions showed potential for additional anti-tumour activity of twice daily dosing at total daily dose below 400?mg, but a loss of efficacy if administered less frequently than once daily. CONCLUSIONS: The proposed model provides a valuable approach for planning future clinical studies and for designing optimized dosing regimens with BYL719. |*Models, Biological [MESH] |Adult [MESH] |Aged [MESH] |Dose-Response Relationship, Drug [MESH] |Enzyme Inhibitors/*administration & dosage/pharmacokinetics/therapeutic use [MESH] |Female [MESH] |Humans [MESH] |Male [MESH] |Middle Aged [MESH] |Neoplasms/*drug therapy/pathology [MESH] |Nonlinear Dynamics [MESH] |Phosphoinositide-3 Kinase Inhibitors [MESH] |Thiazoles/*administration & dosage/pharmacokinetics/therapeutic use [MESH]Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoi(epmc).pdf DeepDyve Pubget Overpricing