ArticleBMC clinical pharmacology2003
The pharmacokinetics of the interstitial space in humans.
Article in BMC clinical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams.Critical care (London, England) · 2011Pooled it
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- Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.BioMed research international · 2020Review
- Simultaneous Assessment of Hepatic Transport and Metabolism Pathways with a Single Probe Using Individualized PBPK Modeling ofThe Journal of pharmacology and experimental therapeutics · 2019Article
- PKQuest: PBPK modeling of highly lipid soluble and extracellular solutes.ADMET & DMPK · 2019Article
- Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology.The AAPS journal · 2018Article
- Parenteral bilirubin in healthy volunteers: a reintroduction in translational research.British journal of clinical pharmacology · 2018Article
- A Bottom-Up Whole-Body Physiologically Based Pharmacokinetic Model to Mechanistically Predict Tissue Distribution and the Rate of Subcutaneous Absorption of Therapeutic Proteins.The AAPS journal · 2016Article
- Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements.International journal of general medicine · 2016Review
- Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease.Clinical and experimental gastroenterology · 2014Review
- Article
- Measurement of Tissue interstitial volume in healthy patients and those with amyloidosis with equilibrium contrast-enhanced MR imaging.Radiology · 2013Article
- The role of tumor tissue architecture in treatment penetration and efficacy: an integrative study.Frontiers in oncology · 2013Article
- Applications of minimal physiologically-based pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2012Article
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic (PBPK) model applicable to most extracellular solutes.
methodsThe human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphine-6-glucuronide, morphine-3-glucuronide, inulin and beta-lactam antibiotics with a range of protein binding (amoxicillin, piperacillin, cefatrizine, ceforanide, flucloxacillin, dicloxacillin). A PBPK data set was developed for extracellular solutes based on the literature for interstitial organ volumes. The program PKQuest was used to generate the PBPK model predictions. The pharmacokinetics of the protein (albumin) bound beta-lactam antibiotics were characterized by two parameters: 1) the free fraction of the solute in plasma; 2) the interstitial albumin concentration. A new approach to estimating the capillary permeability is described, based on the pharmacokinetics of the highly protein bound antibiotics.
resultsAbout 42% of the total body water is extracellular. There is a large variation in the organ distribution of this water - varying from about 13% of total tissue water for skeletal muscle, up to 70% for skin and connective tissue. The weakly bound antibiotics have flow limited capillary-tissue exchange kinetics. The highly protein bound antibiotics have a significant capillary permeability limitation. The experimental pharmacokinetics of the 11 solutes is well described using the new PBPK data set and PKQuest.
conclusionsOnly one adjustable parameter (systemic clearance) is required to completely characterize the PBPK for these extracellular solutes. Knowledge of just this systemic clearance allows one to predict the complete time course of the absolute drug concentrations in the major organs. PKQuest is freely available http://www.pkquest.com.
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