ArticlePharmaceutical research2003
Prediction of in vivo tissue distribution from in vitro data. 3. Correlation between in vitro and in vivo tissue distribution of a homologous series of nine 5-n-alkyl-5-ethyl barbituric acids.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Drug structure-transport relationships.Journal of pharmacokinetics and pharmacodynamics · 2010Review
- Mechanistic approaches to volume of distribution predictions: understanding the processes.Pharmaceutical research · 2007Article
- Development of a whole body physiologically based model to characterise the pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition ratios.Journal of pharmacokinetics and pharmacodynamics · 2004Article
- Prediction of in vivo tissue distribution from in vitro data. 2. Influence of albumin diffusion from tissue pieces during an in vitro incubation on estimated tissue-to-unbound plasma partition coefficients (Kpu).Pharmaceutical research · 2003Article
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Authors and funding
3 authors.
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Abstract
purposeTo evaluate the ability to determine accurate in vivo tissue-to-unbound plasma distribution coefficients (Kpue) from in vitro data.
methodsFresh pieces of fifteen rat tissues/organs were incubated at 37 degrees C with a homologous series of nine barbiturates covering a wide range of lipophilicity (Log P 0.02 to 4.13). Steady-state in vivo Kpue values were estimated from the tissue and plasma concentrations following simultaneous dosing by constant rate i.v. infusion of all nine barbiturates. Drug concentrations in the tissues and media were determined by HPLC with UV or mass spectrometric detection.
resultsThe pharmacokinetics of the barbiturate series following constant rate i.v. infusion indicated a range of clearance (0.49 to 30 ml x min(-1) x kg(-1)) and volume of distribution at steady state (0.51 to 1.9 l x kg(-1)) values. Good agreement was observed between the in vitro and in vivo Kpu values, although for the most lipophilic barbiturates the in vitro data underpredicted the in vivo tissue distribution for all tissues.
conclusionThe in vitro system for predicting the extent of in vivo tissue distribution works well for compounds of widely differing lipophilicity, although for the most lipophilic drugs it may result in an underprediction of in vivo values.
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