title: Pharmacokinetic modeling and simulation of gastrointestinal transit effects on plasma concentrations of drugs from mixed immediate-release and enteric-coated pellet formulations.
abstract: Effects of gastrointestinal transit on plasma concentrations of drugs from mixed immediate-release and enteric-coated pellet formulation were simulated with models developed by including gastric emptying time and lag time of emptying. Models were evaluated by comparing simulated plasma concentrations of amphetamine from Monte Carlo simulations to available published data of a commercial mixed pellet formulation (Adderall XR). Results show that the plasma profile from the mixed pellet formulation does not mimic that from two immediate-release doses administered at different times. Instead, the plasma profile from the mixed pellets of amphetamine is similar to a typical sustained-release formulation. The pharmacokinetic models presented herein describe plasma concentrations of amphetamine from mixed pellet formulation quite well. The models and assumptions are general and can be applied to other drugs in similar mixed pellet dosage forms.
authors.affiliation: Clinical Pharmacology, PPD, Inc., Richmond, VA 23230-3323, USA. prapoch.watanalumlerd@richmond.ppdi.com
authors.forename: Prapoch
authors.initials: P
authors.lastname: Watanalumlerd
authors.forename: J Mark
authors.initials: JM
authors.lastname: Christensen
authors.forename: James W
authors.initials: JW
authors.lastname: Ayres
mesh_terms: D000662:Amphetamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D018565:Food-Drug Interactions; D005746:Gastric Emptying; D005772:Gastrointestinal Transit; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D012995:Solubility
chemical_list: C090411:Adderall; D000662:Amphetamines; D002214:Capsules; D003692:Delayed-Action Preparations