ArticlePharmaceutical research1999
A physiological pharmacokinetic model for solute disposition in tissues below a topical below a topical application site.
Article in Pharmaceutical research, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 30 citations in OpenAlex.
- In vivo determination of the diclofenac skin reservoir: comparison between passive, occlusive, and iontophoretic application.Drug design, development and therapy · 2015Trial
- Time-Dependent Differences in the Effects of Oleic Acid and Oleyl Alcohol on the Human Skin Barrier.Molecular pharmaceutics · 2023Article
- Visualization of Epidermal Reservoir Formation from Topical Diclofenac Gels by Raman Spectroscopy.Journal of pain research · 2020Article
- Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters.The AAPS journal · 2017Article
- Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application.British journal of clinical pharmacology · 2012Article
- Drug structure-transport relationships.Journal of pharmacokinetics and pharmacodynamics · 2010Review
- The effects of equine skin preparation on transdermal drug penetration in vitro.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2006Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMany compounds are applied to the skin with the aim of targeting deeper underlying tissues. This work sought to define the pharmacokinetics of solutes in tissues below a topical application site in terms of perfusate binding, tissue binding and perfusate flow rate.
methodsThe disposition kinetics of diclofenac in a single pass perfused limb preparation after dermal application disposition was studied using dextran and bovine serum albumin (BSA) containing perfusates. A pharmacokinetic model was then developed to relate the tissue retention half lives for diclofenac, diazepam, water, lignocaine and salicylate to their fraction unbound in the tissues, their fraction unbound in the perfusate and the perfusate flow rate.
resultsDiclofenac had estimated tissue retention half lives of 18.1 hr and 3.5 hr for the dextran and BSA containing perfusates, respectively. The fraction of diclofenac and other solutes unbound in the tissues correlated with their corresponding fraction unbound in the perfusate. The tissue retention half lives for diclofenac and other solutes could be described in terms of the fraction of solute unbound in the tissues and perfusate, together with the flow rate.
conclusionThe tissue pharmacokinetics of solutes below a topical application are a function of their binding in the tissues, binding in perfusate and local blood flow.
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Registered trials
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.