title: Development of a Level A in Vitro-in Vivo Correlation for Veliparib (ABT-888) Extended Release Tablet Formulation.
abstract: The aim of the current manuscript is to develop and validate a level A in vitro-in vivo correlation (IVIVC) for veliparib extended-release (ER) tablet formulations.
  
  
  
  The in vitro release profiles of veliparib formulations were determined using USP Dissolution Apparatus 2 with 900 mL of 0.1 N HCl at 75 rpm. In a clinical study, 24 subjects with solid tumors received one of the ER formulations (200 mg): fast (Formulation A), intermediate (Formulation B), and slow (Formulation C), and two 100 mg immediate release capsules (Formulation D). Blood samples were collected over a period of 48 h and analyzed using LCMS/MS. A linear correlation model was developed using fraction absorbed and fraction dissolved data from formulations A and B. Besides assessing internal predictability, external predictability was evaluated using formation C. Prediction errors were estimated for maximum observed plasma concentration (Cmax) and area under the plasma-concentration time curve from zero to last measured time point (AUCt) to determine the predictive ability of the correlation.
  
  
  
  There was a significant linear relationship (r2= 0.944) between the fraction of drug absorbed and the fraction of drug dissolved. The prediction error using the internal validation for Cmaxand AUCtwere below 15% for the individual formulations and below 10% for the average. The prediction error in AUCtand Cmaxfor formulation C was 5% and 11%, respectively.
  
  
  
  A level A IVIVC for the veliparib ER tablet formulation was established. The IVIVC may allow the associated dissolution data to be used as a surrogate for bioavailability.
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1N Waukegan Road, AP31-3, North Chicago, Illinois, 60064, USA. rajendar.mittapalli@abbvie.com.
authors.forename: Rajendar K
authors.initials: RK
authors.lastname: Mittapalli
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1N Waukegan Road, AP31-3, North Chicago, Illinois, 60064, USA.
authors.forename: Silpa
authors.initials: S
authors.lastname: Nuthalapati
authors.affiliation: Process Engineering Sciences, Drug Product Development AbbVie Inc.,, North Chicago, Illinois, USA.
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Delke DeBord
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1N Waukegan Road, AP31-3, North Chicago, Illinois, 60064, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D018565:Food-Drug Interactions; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry; D016014:Linear Models; D009369:Neoplasms / Q000188:drug therapy; D012995:Solubility; D013607:Tablets
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D003692:Delayed-Action Preparations; D013607:Tablets; C521013:veliparib; D065347:Hypromellose Derivatives
keywords: dissolution; extended-release formulation; in vitro/in vivo correlations (IVIVC); pharmacokinetics; veliparib