Abstract：
:Toxicokinetics is the assessment of systemic exposure in toxicity studies, in which pharmacokinetic data are generated, either as an integral component in the conduct of the nonclinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. The data may be used in the interpretation of toxicity findings and contribute to the assessment of the relevance of these findings to clinical safety. Data may be obtained from all animals in a toxicity study, in representative subgroups, in satellite groups or in separate studies. Applying a mixed effects modelling approach in toxicokinetics offers many advantages over the current approach of having satellite groups. Sparse samples for measuring drug/metabolite concentration are collected in all main animals in the majority of studies where toxicological findings are obtained. Such sampling is unlikely to distress the animals, disturb the conduct of a toxicological study or affect the outcome of the study. Many of the outcome measures in toxicological studies are categorical in nature. For example, lesions may be scored on a one to four scale, from none to severe. The analysis of such data is usually carried out using a general mixed modelling approach. We have implemented such models in a nonlinear mixed effects modelling framework which allows us to relate pharmacokinetic response to outcome. A case study is used to illustrate the principles of general mixed effects modelling in toxicokinetics.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Aarons L,Graham Gdoi
10.1016/s0378-4274(01)00272-7keywords:
subject
Has Abstractpub_date
2001-03-31 00:00:00pages
405-10issue
1-3eissn
0378-4274issn
1879-3169pii
S0378-4274(01)00272-7journal_volume
120pub_type
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journal_title：Toxicology letters
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pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90172-7
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.04.035
更新日期：2004-09-25 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：
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journal_title：Toxicology letters
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journal_title：Toxicology letters
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journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章
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更新日期：1988-07-01 00:00:00
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pub_type： 杂志文章
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更新日期：1998-11-23 00:00:00
abstract：:Paraquat poisoning results in damages of multiple organs including liver, kidney and lung, and antioxidants have been proven to have protective effects. As a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was introduced to clinical use recently, its protective effect was studied on acute ...
journal_title：Toxicology letters
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更新日期：2003-06-05 00:00:00
