title: Disease specific modeling: Simulation of the pharmacokinetics of meloxicam and ibuprofen in disease state vs. healthy conditions.
abstract: OBJECTIVE
  Studies have shown altered pharmacokinetic patterns (PK) in patient suffering from acute pain. Thus, we aimed to simulate pharmacokinetics of meloxicam and ibuprofen in pain and pain-free states using a physiological based software program to identify the underlining mechanistic changes for the observed differences.
  
  
  METHODS
  Published in vivo data of meloxicam and ibuprofen were used for the simulations. Two drug formulations were studied: a fast dissolving (FD) and regular release (RR) tablet formulation. The oral bioavailability was compared between these formulations in vagally suppressed rats (gastric dysfunction) and a control group. For ibuprofen additional human data of a control and post dental surgery group were used. All simulations were performed using GastroPlus™. The in vivo drug release and PK of all formulations were estimated for both drugs using the software's immediate release (IR) or gastric release (GR) models.
  
  
  RESULTS
  For meloxicam, the IR model predicted the in vivo absorption in the control group after administration of the FD and RR formulations. When gastric dysfunction was induced, the IR model did not predict absorption while the GR model did for both formulations, FD and RR. For ibuprofen, the predictions were also very close for both formulations, using the IR model for the control group and the GR model for the vagally suppressed condition in rats and humans.
  
  
  CONCLUSIONS
  Gastric control of the drug release in pain/disease state was identified as the major factor causing the observed differences in the pharmacokinetics. Computer simulations of disease states can be employed to optimize drug release from dosage forms to overcome the reported shortfalls in the drug absorption.
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: May
authors.initials: M
authors.lastname: Almukainzi
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Aghazadeh-Habashi
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Science, University of Alberta, Edmonton, AB, Canada. Electronic address: raimar.loebenberg@ualberta.ca.
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004195:Disease Models, Animal; D006801:Humans; D007052:Ibuprofen / Q000493:pharmacokinetics*; D000077239:Meloxicam; D051381:Rats; D013607:Tablets; D013843:Thiazines / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000493:pharmacokinetics*
chemical_list: D013607:Tablets; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam; D007052:Ibuprofen
keywords: ACAT; Bioequivalence; Dissolution; Gastric dysfunction; Gastric release; GastroPlus; Ibuprofen; Meloxicam; Pain; Simulation