ArticleJournal of pharmacokinetics and pharmacodynamics2004
Development of a whole body physiologically based model to characterise the pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition ratios.
Article in Journal of pharmacokinetics and pharmacodynamics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Linking preclinical and clinical whole-body physiologically based pharmacokinetic models with prior distributions in NONMEM.European journal of clinical pharmacology · 2007Trial
- Exploring the Pharmacokinetic Mysteries of the Liver: Application of Series Compartment Models of Hepatic Elimination.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Article
- Whole body physiologically based modelling of β-blockers in the rat: events in tissues and plasma following an i.v. bolus dose.British journal of pharmacology · 2018Article
- Evaluation and calibration of high-throughput predictions of chemical distribution to tissues.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Use of partition coefficients in flow-limited physiologically-based pharmacokinetic modeling.Journal of pharmacokinetics and pharmacodynamics · 2012Article
- Drug structure-transport relationships.Journal of pharmacokinetics and pharmacodynamics · 2010Review
- Physiologically based pharmacokinetic modeling of drug disposition in rat and human: a fuzzy arithmetic approach.Pharmaceutical research · 2008Article
- Mechanistic approaches to volume of distribution predictions: understanding the processes.Pharmaceutical research · 2007Article
- A comment on the application of drug tissue-plasma partition coefficients K(p) in eliminating organs to calculation of volume of distribution at steady state.Journal of pharmacokinetics and pharmacodynamics · 2005Article
- A comment on the "correction" of tissue-plasma partition coefficients for drug extraction in eliminating organs by Sven Björkman.Journal of pharmacokinetics and pharmacodynamics · 2005Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three methods for estimation of the equilibrium tissue-to-plasma partition ratios (Kp values) in the presence of tissue concentration time data have been investigated. These are the area method, the open loop (tissue specific) method and the whole body model(closed loop) method, each with different model assumptions. Additionally, multiple imputations, a technique for dealing with deficiencies in data sets (i.e., missing tissues) is used. The estimated Kp values by the three methods have been compared and the limitations and advantages of each approach drawn. The area method, which is essentially model free, gives only a crude estimate of Kp without making any statement of its uncertainty; whereas both the open and closed loop methods provide an estimate of this. The closed loop method, where the most assumptions are made, is the approach that gives the best overall estimates of Kp, which was confirmed by comparing the predicted concentration-time profiles with experimental data. Although the estimates from the closed loop method, as well as the other two methods, are conditioned on the data, they are the most reliable for both propagating parameter variability and uncertainty through a whole body physiologically based model, as well as for extrapolation to human. A series of benzodiazepines, namely alprazolam, chlordiazepoxide, clobazam, diazepam, flunitrazepam, midazolam and triazolam in rat is used as a case study in the current investigation.
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