Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Alirocumab and evolocumab are 2 human monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9). These antibodies can potently lower low-density lipoprotein cholesterol (LDLc) serum concentrations. The aims of this analysis were to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for both antibodies, to simulate and investigate different dosage and application regimens, and finally, to note the effects on LDLc levels. Alirocumab was clinically studied and approved with 2 doses, 75 and 150 mg every 2 weeks (Q2W), whereas evolocumab was tested and approved with 2 dosing intervals, 140 mg Q2W and 420 mg Q4W. Data were digitized from published studies describing alirocumab and evolocumab PK, as well as LDLc levels in humans for various single and multiple doses. Alirocumab dosages ranged between 75 and 300 mg and evolocumab from 7 to 420 mg. The analysis was performed using a nonlinear mixed-effects modeling technique. A 2-compartment model with first-order absorption and saturable elimination described the PK of both antibodies best. LDLc levels were described by a turnover model with zero-order synthesis rate decreased by the antibodies and a first-order degradation rate that was increased by the antibodies. Simulations show a comparable effectiveness for alirocumab 75 mg Q2W and 150 mg Q3W as well as evolucmab 140 mg Q2W and 420 mg Q5W, respectively. This is the first PK/PD model describing the link between alirocumab and evolocumab PK and LDLc concentrations. The model may serve as an important tool to simulate different dosage regimens in order to optimize therapy.
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Source |
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http://dx.doi.org/10.1002/jcph.866 | DOI Listing |
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