ArticleBMC clinical pharmacology2002
PKQuest: capillary permeability limitation and plasma protein binding - application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics.
Article in BMC clinical pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Heterogeneity of human adipose blood flow.BMC clinical pharmacology · 2007Trial
- PKQuest: PBPK modeling of highly lipid soluble and extracellular solutes.ADMET & DMPK · 2019Article
- Applied Concepts in PBPK Modeling: How to Build a PBPK/PD Model.CPT: pharmacometrics & systems pharmacology · 2016Article
- Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease.Clinical and experimental gastroenterology · 2014Review
- Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood.BMC clinical pharmacology · 2010Article
- PKQuest_Java: free, interactive physiologically based pharmacokinetic software package and tutorial.BMC research notes · 2009Article
- Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat.BMC clinical pharmacology · 2006Article
- Human physiologically based pharmacokinetic model for propofol.BMC anesthesiology · 2005Article
- Physiologically based pharmacokinetic modeling of arterial - antecubital vein concentration difference.BMC clinical pharmacology · 2004Article
- The pharmacokinetics of the interstitial space in humans.BMC clinical pharmacology · 2003Article
- The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorption.BMC clinical pharmacology · 2003Article
- PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol.BMC clinical pharmacology · 2002Article
- PKQuest: volatile solutes - application to enflurane, nitrous oxide, halothane, methoxyflurane and toluene pharmacokinetics.BMC anesthesiology · 2002Article
- PKQuest: measurement of intestinal absorption and first pass metabolism - application to human ethanol pharmacokinetics.BMC clinical pharmacology · 2002Article
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1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may not be valid if there is a large amount of plasma protein binding because the effective capillary permeability depends on the product of the intrinsic capillary permeability (PS) and the fraction of solute that is free in the blood (fwB). PKQuest, a new generic physiologically based pharmacokinetic software routine (PBPK), provides a novel approach to modeling capillary permeability in which the only adjustable parameter is the PS of muscle.
methodsAll the results were obtained by applying PKQuest to previously published human pharmacokinetic data.
resultsThe PKQuest analysis suggests that the highly protein bound antibiotics dicloxacillin and ceftriaxone have a significant capillary permeability limitation. The human muscle capillary PS of inulin, dicloxacillin and ceftriaxone was 0.6, 13 and 6 ml/min/100 gm, respectively. The ceftriaxone protein binding is non-linear, saturating at high plasma concentrations. The experimental ceftriaxone data over a wide range of intravenous inputs (0.15 to 3 gms) was well described by PKQuest. PKQuest is the first PBPK that includes both permeability limitation and non-linear binding.
conclusionsBecause of their high degree of plasma protein binding, dicloxacillin and ceftriaxone appear to have a diffusion limited exchange rate between the blood and tissue and are not flow limited as had been previously assumed. PKQuest and all the examples are freely available at http:\\www.pkquest.com.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.