title: Prediction of in-vivo iontophoretic drug release data from in-vitro experiments-insights from modeling.
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.
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark NJ 0702, USA. Electronic address: laurent.simon@njit.edu.
authors.forename: Laurent
authors.initials: L
authors.lastname: Simon
authors.affiliation: Logic and Computation Group, Physics Engineering Program, School of Sciences and Humanities, EAFIT University, Medellin, Colombia.
authors.forename: Juan
authors.initials: J
authors.lastname: Ospina
authors.affiliation: College of Pharmacy, Touro University Mare Island-Vallejo, California 94592, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ita
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D003198:Computer Simulation; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D065546:Drug Liberation; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D055641:Mathematical Concepts; D008954:Models, Biological; D009270:Naloxone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D012869:Skin Absorption
chemical_list: C079704:dexamethasone-21-sulfobenzoate; D000639:Amitriptyline; D009270:Naloxone; D003907:Dexamethasone; D013007:Growth Hormone-Releasing Hormone
keywords: Closed-form solution; Controlled release; In-vivo in-vitro correlation; Iontophoresis; Laplace transform