title: Validation of Computational Approaches for Antiretroviral Dose Optimization.
abstract: Strategies for reducing antiretroviral doses and drug costs can support global access, and numerous options are being investigated. Efavirenz pharmacokinetic simulation data generated with a bottom-up physiologically based model were successfully compared with data obtained from the ENCORE I clinical trial (efavirenz at 400 mg once per day versus 600 mg once per day). These findings represent a pivotal paradigm for the prediction of pharmacokinetics resulting from dose reductions. Validated computational models constitute a valuable resource for optimizing therapeutic options and predicting complex clinical scenarios.
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom siccardi@liverpool.ac.uk.
authors.forename: Marco
authors.initials: M
authors.lastname: Siccardi
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Dickinson
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D048588:Benzoxazines / Q000493:pharmacokinetics* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D015870:Gene Expression; D006678:HIV / Q000187:drug effects / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D059645:Mutation Rate
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz