Prediction of in-vivo iontophoretic drug release data from in-vitro experiments-insights from modeling

Laurent Simon, Juan Ospina, Kevin Ita

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A strategy was developed to predict in-vivo plasma drug levels from data collected during in-vitro transdermal iontophoretic delivery experiments. The method used the principle of mass conservation and the Nernst-Planck flux equation to describe molecular transport across the skin. Distribution and elimination of the drug in the body followed a one- or two-compartment open model. Analytical expressions for the relaxation constant and plasma drug concentration were developed using Laplace transforms. The steady-state dermal flux was appropriate for predicting drug absorption under in-vivo conditions only when the time constant in the skin was far greater than its value in the blood compartment. A simulation study was conducted to fully assess the performance of estimations based on the equilibrium flux approximation. The findings showed that the normalized integral of squared error decreased exponentially as the ratio of the two time constants (blood/skin) increased. In the case of a single compartment, the error was reduced from 0.15 to 0.016 when the ratio increased from 10 to 100. The methodology was tested using plasma concentrations of a growth-hormone releasing factor in guinea pigs and naloxone in rats.

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalMathematical Biosciences
Volume270
DOIs
StatePublished - Dec 2015

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Keywords

  • Closed-form solution
  • Controlled release
  • In-vivo in-vitro correlation
  • Iontophoresis
  • Laplace transform

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