User:Jdibella79/New article

Simulations Plus, a company based in Lancaster, California, USA, develops Absorption, Distribution, Metabolism and Excretion (ADME) modeling and simulation software for the pharmaceutical and biotechnology industries. The programs target different stages of the drug development process.

GastroPlus is a physiologically-based simulation tool that predicts the absorption and pharmacokinetics for drugs administered intravenously or orally. The underlying model is the Advanced Compartmental Absorption and Transit (ACAT) model - an extension of work originally done by Gordon Amidon and Lawrence Yu^[1]. Simulations consist of the numerical integration of differential equations that coordinate a set of well-characterized physical phenomena that occur and interact as a result of drug transport, dissolution/precipitation, lumenal degradation, absorption/exsorption, excretion, gut metabolism, distribution, hepatic metabolism, enterohepatic circulation, renal clearance, and other clearance mechanisms. Researchers at various pharmaceutical companies and academic sites utilize GastroPlus in a variety of drug discovery and drug development activities ^[2]^[3]^[4]^[5]

ADMET Predictor is a modeling program that enables pharmaceutical researchers to estimate ADMET properties (such as pKa(s), permeability, solubility, lipophilicity, diffusivity, metabolic inhibition, toxicities, etc...) of new chemical entities from their molecular structure. The performance of the models have been assessed in several articles^[6]^[7]. ADMET Modeler, an integrated feature in ADMET Predictor, allows scientists to build predictive structure-property models using their own data.

ClassPharmer is a multi-purpose cheminformatics software tool used for screening data analysis, hit-to-lead development, de novo design, and lead optimization^[8].

DDDPlus is a software tool for formulation scientists that simulates the in vitro disintegration and dissolution of solid dosage forms under different experimental conditions.

Currently, 18 of the top 20 pharmaceutical companies license the company's software. Simulations Plus also offers consultancy services on a wide range of issues (predict first-in-man pharmacokinetic outcomes (F%, Cmax, AUC, Cp-time profiles) from available in vitro and preclinical data, assess different formulation strategies to enhance the dissolution and/or absorption of a drug, simulate a virtual clinical trial, incorporating variability for the physiological, formulation, and pharmacokinetic parameters, to generate a population outcome, etc...).

References

^ Yu, L.X., Lipka, E., Crison, J.R., Amidon, G.L. (1996a) “Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption” Adv. Drug Del. Rev. 19:359–76.
^ Dannenfelser RM, He H, Joshi Y, Bateman S, Serajuddin AT. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004 May;93(5):1165-75.
^ Kuentz M, Nick S, Parrott N, Röthlisberger D. A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur J Pharm Sci. 2006 Jan;27(1):91-9.
^ De Buck SS, Sinha VK, Fenu LA, Nijsen MJ, Mackie CE, Gilissen RA. Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs. Drug Metab Dispos. 2007 Oct;35(10):1766-80.
^ Tubic-Grozdanis M, Bolger MB, Langguth P. Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds. AAPS J. 2008;10(1):213-26.
^ Dearden, J.C.. "In silico prediction of aqueous solubility." Expert Opin. Drug Discov 1(2006): 31-52, 2006.
^ Tetko, I. V. and Poda, G. I. "Property-based logP prediction." In: R. Mannhold (ed.), Molecular Drug Properties: Measurement and Prediction, pp. Chapter 15. Weinheim, Germany: Wiley-VCH, 2007.
^ Schnur, D.M., Hermsmeier, M.A., and Tebben, A.J. Are Target-Family-Privileged Substructures Truly Privileged? J. Med. Chem., 49, 6, 2000 - 2009, 2006, 10.1021/jm0502900

[1] Yu, L.X., Lipka, E., Crison, J.R., Amidon, G.L. (1996a) “Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption” Adv. Drug Del. Rev. 19:359–76.

[2] Dannenfelser RM, He H, Joshi Y, Bateman S, Serajuddin AT. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004 May;93(5):1165-75.

[3] Kuentz M, Nick S, Parrott N, Röthlisberger D. A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur J Pharm Sci. 2006 Jan;27(1):91-9.

[4] De Buck SS, Sinha VK, Fenu LA, Nijsen MJ, Mackie CE, Gilissen RA. Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs. Drug Metab Dispos. 2007 Oct;35(10):1766-80.

[5] Tubic-Grozdanis M, Bolger MB, Langguth P. Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds. AAPS J. 2008;10(1):213-26.

[6] Dearden, J.C.. "In silico prediction of aqueous solubility." Expert Opin. Drug Discov 1(2006): 31-52, 2006.

[7] Tetko, I. V. and Poda, G. I. "Property-based logP prediction." In: R. Mannhold (ed.), Molecular Drug Properties: Measurement and Prediction, pp. Chapter 15. Weinheim, Germany: Wiley-VCH, 2007.

[8] Schnur, D.M., Hermsmeier, M.A., and Tebben, A.J. Are Target-Family-Privileged Substructures Truly Privileged? J. Med. Chem., 49, 6, 2000 - 2009, 2006, 10.1021/jm0502900

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