Oral bioavailability of blockbuster drugs in humans and animals




    Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor. It was first approved in 2004 by the FDA. In 2011 it was on rank nine of the most selling drugs in the U.S. market and achieved a total sales of US$ 3552 million.

    In 2012 and 2013 the blockbuster Duloxetine was on rank five of the most selling drugs in the U.S. market and achieved sales of US$ 4473 million and US$ 5083 million, respectively.

    An analysis of all records in PACT-F about duloxetine showed large species differences in oral bioavailability between humans, rats and dogs:

    Mudaliar, M. Bioequivalence comparison of generic drug DuLocap and brand drug Cymbalta. J Med Investig Pract 9, 79-84 (2014)
    European Medicines Agency: Duloxetine, Scientific discussion, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000552/WC500026745.pdf, May 2016

    Ethical and financial reasons speak against the use of drug-uptake experiments in animals. Alternative computational methods, such as the expert system IMPACT-F are now available and replace animal trials on drug-uptake. Pharmaceutical companies have applied the expert system to evaluate human oral bioavailability in various therapeutic areas such as diabetes, inflammation, antivirals, autoimmune diseases and cancer.

    The expert system evaluates oral bioavailability in humans significantly more reliably than animal trials. This further increases the prospects of human clinical trials, because optimum oral dose for first-in-human clinical trials can be determined much more accurately. Efficacy issues are identified as the main reason why clinical trials in humans fail.

    Animal trials can hamper drug discovery and development: Top selling drugs, including the most sold blockbuster drugs of 2013, would not have been developed if scientists had relied solely on bioavailability trials in animals.

    Furthermore it raises the question, which other blockbuster drugs would be on the market today, if animal trials would have not been used to preselect compounds and drug-candidates for further development?

    An evaluation with the expert system identifies, if back-up compounds or drug-candidates, which previously were rejected because of low animal bioavailability, would possess oral bioavailability in humans and could be further developed to oral medications.

    Dr. Wolfgang Boomgaarden
    Founder and CEO of PharmaInformatic

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Top Selling Drugs having sales
in excess of
US-$ one billion
in a year
such as

No.1 in 2013
US$ 6294 million

No.2 in 2013
US$ 5975 million

No.5 in 2013
US$ 5083 million

Drugs.com Statistics, U.S. Pharmaceutical Sales - 2013 (Link).

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