Frontiers in Drug Design and Discovery

Volume: 4

New Sampling Techniques for Pharmacokinetic- Pharmacodynamic Modeling

Author(s): Christian Höcht, Marcos Mayer, Javier A.W. Opezzo, Guillermo F. Bramuglia and Carlos A. Taira

Pp: 43-80 (38)

DOI: 10.2174/978160805202810904010043

* (Excluding Mailing and Handling)

Abstract

Considering that pharmacokinetic-pharmacodynamic (PK-PD) modeling describes the relationship between tissue concentrations of drugs and their corresponding pharmacological response, an important issue of PK-PD studies is the availability of powerful sampling techniques that allow measurement of tissue concentrations of drugs at multiple time points. Traditional sampling techniques, including biopsy, blood and saliva sampling, and skin blister sampling, have several limitations for drug monitoring during PK-PD studies, considering that these techniques did not allow the measurement of drug concentrations at the site of action. In the last decades, new sampling techniques, including membrane based techniques (microdialysis and ultrafiltration) and imaging techniques (positron emission tomography and magnetic resonance spectroscopy), have been available for measurement of drug concentration at the target site. The possibility of simultaneous monitoring of target site concentrations of drugs and their pharmacological effect with these new sampling techniques have significantly improves current knowledge of PK-PD modeling. In addition, membrane based techniques also allow simultaneous monitoring of endogenous compounds and therefore permit the study of the relationship between drug target site concentrations and their effect on biochemical markers, making these techniques highly useful for PK-PD modeling studies. The aim of this chapter is to describe the principles of membrane based techniques and imaging techniques, and their applicability for drug monitoring in PK-PD modeling.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1740515339 and j.to_date >= 1740515339 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2200) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1740515339 and j.to_date >= 1740515339 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2200) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1740515339 and j.to_date >= 1740515339 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2200)
      660μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 945 and `b`.`banner_from_date` <= 1740515339 and `b`.`banner_to_date` >= 1740515339 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 945
      • 3: 1740515339
      • 4: 1740515339
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='bfd83791b9f7b6850e205bf54d1d2c06'
      270μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        6GPPFvWxaVYycXyNxt7tTFT1Px3bWC5tzFWz0zox
        uc_cart_id
        bfd83791b9f7b6850e205bf54d1d2c06
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2200" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/2200
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ik1qZmZoT0hRNWF1bTd3YXJUemgrRmc9PSIsInZhbHVlIjoiY3h0aGNjTHhyZmcrbFkxZ0JUQzMxaU5XWlBTdXBwVGdLZUpYZDY3d3Uwaz0iLCJtYWMiOiI4NmEyODU0ZjAwZGI0NzU0MmQxNTc1ZjFhNjdkMjUyZjdlZGYyZDE1NzhmOGE3MDA1NDJjMThmYjYxY2YwNDAzIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ik1qZmZoT0hRNWF1bTd3YXJUemgrRmc9PSIsInZhbHVlIjoiY3h0aGNjTHhyZmcrbFkxZ0JUQzMxaU5XWlBTdXBwVGdLZUpYZDY3d3Uwaz0iLCJtYWMiOiI4NmEyODU0ZjAwZGI0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 20:28:59 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IllibG1PY0JrTHlWVlBrSGVEb0h0dlE9PSIsInZhbHVlIjoiMVVwU2JpTTNnN3FyQlNuM3ZORXFMSFk3cGF1V3VvRmE5bVI5ZEk5a3hsWjdNWWhKdVJMNnpkNENoeS9jZ0ZKR01kdXd5MmN0bmw3aEo2R1VhZHl2Ulp0emRhc2NkTDdKb29OVGZKbmd4Mkl1UEp0RGhpS0c2bGxqNWZTNU8yanMiLCJtYWMiOiIwZTBlNjJkMDY5MGI4ZWU5YWM3YWZkNWUwYjIwNmJmNzg0MTE5MDk1MDA0MzZjYTZlM2U2NjE1ODk1YzhlNzEwIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:28:59 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IllibG1PY0JrTHlWVlBrSGVEb0h0dlE9PSIsInZhbHVlIjoiMVVwU2JpTTNnN3FyQlNuM3ZORXFMSFk3cGF1V3VvRmE5bVI5ZEk5a3hsWjdNWWhKdVJMNnpkNENoeS9jZ0ZKR01kdXd5M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFkWURhRkFqazZyeXFMYU53cnlJZEE9PSIsInZhbHVlIjoiZDR3KzRDRnoxdkRuRTdraGpnUDRZcGpQbG9LSFRpNzVtMFQwa1hBZitMaEJQSDRxL1Z5cS9NSWNrOUZyUytnK1AvKzVLYUpEUjM2U2hpM3pJTnNoY1c0Qmd3THQ5QW8yU1hySXRnbitqTXBBOGZ0Sy9IaExvZVFCNmpaNjR6T1oiLCJtYWMiOiI2ODM0NzdjMzM1MjIwMWQ3ODIzYjI0OTlkYTNjZWVkMzZlNmUzNDNiMzc1MTQ1OTQ0ODI2NDg2YmZkN2FmOGIyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkFkWURhRkFqazZyeXFMYU53cnlJZEE9PSIsInZhbHVlIjoiZDR3KzRDRnoxdkRuRTdraGpnUDRZcGpQbG9LSFRpNzVtMFQwa1hBZitMaEJQSDRxL1Z5cS9NSWN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IllibG1PY0JrTHlWVlBrSGVEb0h0dlE9PSIsInZhbHVlIjoiMVVwU2JpTTNnN3FyQlNuM3ZORXFMSFk3cGF1V3VvRmE5bVI5ZEk5a3hsWjdNWWhKdVJMNnpkNENoeS9jZ0ZKR01kdXd5MmN0bmw3aEo2R1VhZHl2Ulp0emRhc2NkTDdKb29OVGZKbmd4Mkl1UEp0RGhpS0c2bGxqNWZTNU8yanMiLCJtYWMiOiIwZTBlNjJkMDY5MGI4ZWU5YWM3YWZkNWUwYjIwNmJmNzg0MTE5MDk1MDA0MzZjYTZlM2U2NjE1ODk1YzhlNzEwIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:28:59 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IllibG1PY0JrTHlWVlBrSGVEb0h0dlE9PSIsInZhbHVlIjoiMVVwU2JpTTNnN3FyQlNuM3ZORXFMSFk3cGF1V3VvRmE5bVI5ZEk5a3hsWjdNWWhKdVJMNnpkNENoeS9jZ0ZKR01kdXd5M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFkWURhRkFqazZyeXFMYU53cnlJZEE9PSIsInZhbHVlIjoiZDR3KzRDRnoxdkRuRTdraGpnUDRZcGpQbG9LSFRpNzVtMFQwa1hBZitMaEJQSDRxL1Z5cS9NSWNrOUZyUytnK1AvKzVLYUpEUjM2U2hpM3pJTnNoY1c0Qmd3THQ5QW8yU1hySXRnbitqTXBBOGZ0Sy9IaExvZVFCNmpaNjR6T1oiLCJtYWMiOiI2ODM0NzdjMzM1MjIwMWQ3ODIzYjI0OTlkYTNjZWVkMzZlNmUzNDNiMzc1MTQ1OTQ0ODI2NDg2YmZkN2FmOGIyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkFkWURhRkFqazZyeXFMYU53cnlJZEE9PSIsInZhbHVlIjoiZDR3KzRDRnoxdkRuRTdraGpnUDRZcGpQbG9LSFRpNzVtMFQwa1hBZitMaEJQSDRxL1Z5cS9NSWN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "6GPPFvWxaVYycXyNxt7tTFT1Px3bWC5tzFWz0zox" "uc_cart_id" => "bfd83791b9f7b6850e205bf54d1d2c06" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2200" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:28:59GET/chapter/2200112192