Pre-clinical development 1131357 219891209 2008-06-17T09:44:44Z 123.176.40.144 '''Pre-clinical development''' is a stage in the begins before [[clinical trial]]s (testing in humans) can begin, and during which important safety and [[pharmacology]] data is collected. The main goals of pre-clinical studies (also named preclinical studies and nonclinical studies) are to determine a drug's [[pharmacodynamics]] (PD), [[pharmacokinetics]] (PK), [[ADME]], and toxicity through [[in vivo|animal testing]]. This data allows researchers to [[Allometry|allometrically]] estimate a safe starting dose of the drug for [[clinical trial]]s in humans. Pre-clinical studies must adhere to [[Good Laboratory Practice]]s (GLP) in [[ICH]] Guidelines to be acceptable for submission to regulatory agencies such as the [[Food & Drug Administration]] in the United States. Typically, both ''[[in vitro]]'' and ''[[in vivo]]'' tests will be performed. Studies of a drug's [[toxicity]] include which organs are targeted by that drug, as well as if there are any long-term [[carcinogenic]] effects or toxic effects on mammalian [[reproduction]]. The information collected from these studies is vital so that safe human testing can begin. Typically, animal testing involves two species. The most commonly used models are [[Murinae|murine]] and [[Beagle|canine]], although [[macaque|primate]] and [[pig|porcine]] are also used. The choice of species is based on which will give the best correlation to human trials. Differences in the [[Gastrointestinal tract|gut]], [[enzyme activity]], [[circulatory system]], or other considerations make certain models more appropriate based on the [[dosage form]], site of activity, or noxious [[metabolites]]. For example, canines may not be good models for solid oral dosage forms because the characteristic carnivore intestine is underdeveloped compared to the omnivore's, and gastric emptying rates are increased. Also, rodents can not act as models for antibiotic drugs because the resulting alteration to their intestinal flora causes significant [[Adverse effect (medicine)|adverse effects]].1 Depending on a drugs functional groups, it may be metabolized in similar or different ways between species, which will effect both efficacy and toxicology. Based on pre-clinical trials, No Observable Effect Levels (NOEL) on are established, which are used to determine initial phase 1 clinical trial dosage levels on a mass [[Active ingredient|API]] per mass patient basis. Generally a 1/100 uncertainty factor or "safety margin" is included to account for interspecies (1/10) and inter-individual (1/10) differences).2 [[Animal testing]] in the research-based pharmaceutical industry has been reduced in recent years both for ethical and cost reasons. ==See also== *[[Drug Discovery Hit to Lead]] *[[Drug development]] *[[Nonclinical studies]] *[[Pharmacodynamics]] *[[Pharmacokinetics]] *[[ADME|Absorption, Distribution, Metabolism, and Excretion]] *[[Simcyp Simulator]] *[[Caco-2]] *[[Pharmaceutical company]] ==Resources== #Martinez, M.N. Interspecies Differences in Physiology and Pharmacology: Extrapolating Preclinical Data to Human Populations. Rogge, M.C. Taft, D.R Preclinical Development Vol 152 2005. ISBN 1-57444-882-X #Amdur, M.O. Doull, J.D. Klaassen, C.D. Toxicology: The Basic Science of Poisons. 1991. ==External links== * [http://www.fda.gov/cder/handbook/preclin.htm FDA requirements Pre-Clinical Research] * [http://www.biomedcode.com BioMedCode Pre-Clinical Research] * [http://www.iris-pharma.com Iris Pharma Pre-Clinical Research in Ophthalmology] [[Category:Pharmaceutical industry]] [[Category:Drug discovery]]