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Development of a Level A in Vitro-in Vivo Correlation for Veliparib (ABT-888) Extended Release Tablet Formulation

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Abstract

Purpose

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.

Methods

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.

Results

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 Cmax and AUCt were below 15% for the individual formulations and below 10% for the average. The prediction error in AUCt and Cmax for formulation C was 5% and 11%, respectively.

Conclusions

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.

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Abbreviations

AUCinf :

Area under the plasma-concentration time curve from zero to infinity

AUCt :

Area under the plasma-concentration time curve from zero to last measured time point

Cmax :

Maximum observed plasma concentration

ER:

Extended-release

IVIVC:

In vitro in vivo correlation

PARP:

Poly (ADP-ribose) polymerase

PE:

Prediction error

Tmax :

Time to maximum observed plasma concentration

T1/2 :

Terminal half-life

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Author information

Authors and Affiliations

  1. Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1N Waukegan Road, AP31-3, North Chicago, Illinois, 60064, USA

    Rajendar K. Mittapalli, Silpa Nuthalapati & Hao Xiong

  2. Process Engineering Sciences, Drug Product Development AbbVie Inc.,, North Chicago, Illinois, USA

    Alyssa E. Delke DeBord

Authors
  1. Rajendar K. Mittapalli
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  2. Silpa Nuthalapati
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  3. Alyssa E. Delke DeBord
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  4. Hao Xiong
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Corresponding author

Correspondence to Rajendar K. Mittapalli.

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Conflict of Interest

This study was sponsored by AbbVie Inc. AbbVie Inc. contributed to the study design; research; data interpretation; and writing, review and approval of the manuscript for publication. Rajendar K Mittapalli, Silpa Nuthalapati, Alyssa Delke DeBord and Hao Xiong are employees of AbbVie Inc. and may hold AbbVie stocks or options.

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Mittapalli, R.K., Nuthalapati, S., Delke DeBord, A.E. et al. Development of a Level A in Vitro-in Vivo Correlation for Veliparib (ABT-888) Extended Release Tablet Formulation. Pharm Res 34, 1187–1192 (2017). https://doi.org/10.1007/s11095-017-2133-3

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  • DOI: https://doi.org/10.1007/s11095-017-2133-3

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