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Filename: drivers/Session_files_driver.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Filename: models/Detail_model.php
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Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: str_replace
File: /var/www/html/application/controllers/Detail.php
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Function: formatAIDetailSummary
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
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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
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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Function: pubMedGetRelatedKeyword
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Function: require_once
Objective: The study sought to investigate the relationship between efavirenz exposure and the CYP2B6 516G-->T(*6) genotype in HIV/AIDS outpatients, using pharmacokinetic modelling and simulation.
Methods: Blood samples where obtained from 74 outpatients treated with a combination regimen including 600 mg efavirenz daily for a duration of at least 3 weeks at clinics in Harare, Zimbabwe. The subjects were genotyped for the major CYP2B6 variant, CYP2B6*6, associated with reduced enzyme activity, using a PCR-RFLP method. Efavirenz plasma concentrations were determined by HPLC-UV. Population pharmacokinetic modelling and simulation of the data were performed in NONMEM VI.
Results: A high allele frequency of the CYP2B6*6 allele of 49% was observed. Efavirenz plasma concentrations were above 4 mg/L in 50% of the patients. Genotype and sex were identified as predictive covariates of efavirenz disposition. Pharmacokinetic parameter estimates indicate that a dose reduction to 400 mg efavirenz per day is possible in patients homozygous for the CYP2B6*6 genotype without compromising therapeutic efficacy.
Conclusion: The CYP2B6*6 allele occurs at a high frequency in people of African origin and is associated with high efavirenz concentrations. Simulations indicate that an a priori 35% dose reduction in homozygous CYP2B6*6 patients would maintain drug exposure within the therapeutic range in this group of patients. Our preliminary results suggest the conduct of a prospective clinical dose optimization study to evaluate the utility of genotype-driven dose adjustment in this population.
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Source |
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http://dx.doi.org/10.1007/s00228-007-0412-3 | DOI Listing |
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