Module 7 Preclinical phase: Drug Safety Evaluation In Vivo, In Vitro Flashcards
This is the phase in which it is being decided whether a drug is ready for clinical trials (the so called move from bench to bedside).
Preclinical Phase
Involves extensive studies that yield preliminary efficacy, toxicity, pharmacokinetic and safety. information.
Preclinical Phase
Wide doses of the drug are tested using:
in vitro (test tube or cell culture)
In vivo (animal experiments).
In silico profiling (using computer models of the drug-target interactions).
Promising drugs often shelved based on rat or dog toxicity.
Research into early formulations tablet capsule or injection.
Preclinical results submitted to regulatory authorities (in the US, to the FDA), as an Investigational New Drug (IND)-needed before move to clinical phase (human trial).
Preclinical Studies
Prior to human clinical trials there are cell studies to look at activity and toxicity.
Then animal studies to look at toxicity and elimination- rat, dog, macaque. Different animals used for different types of studies and different type of drug.
Preclinical Studies
The preclinical _______ tests involves various biological systems and reveals the species-, organ and dose-specific toxic effects of an investigational product.
Toxicity studies
The toxicity of substances can be observed by:
(a) studying the accidental exposures to a substance
(b) in vitro studies using cells/cell lines
(c) in vivo exposure on experimental animals
is a branch of science that deals with toxins and poisons and their effects and treatment.
Toxicology
is very important for the development of new drugs and for the extension of the therapeutic potential of existing molecules.
Toxicological screening
The US Food and Drug Administration (FDA) states that it is essential to screen new molecules for pharmacological activity and toxicity potential in animals (______).
21CFR Part 314
The history of toxicity studies begins with _____ (1493-1541), who determined specific chemicals responsible for the observed toxicity of plants and animals.
(Father of toxicology)
He demonstrated the harmless and beneficial effects of toxins and proved dose-response relationships for the effects of drugs.
“All substances are poisons, there is none which is not poison. The right dose differentiates a poison and a remedy”
Paracelsus
A Spanish Physician, determined the relationship between poisons and their biological properties and demonstrated specific organ damage caused by toxins.
“Father of Modern Toxicology”
Mathieu Orfila, (1787-1853)
proposed the use of the 50% lethal dose (LD) test to determine the lethal dose of individual chemicals.
Initiates the use of animals for toxicity studies
J. W. Trevan (1920)
developed a method for testing eye and skin irritation using rabbits, and this method was widely accepted for testing the effects of chemicals and pharmaceuticals on the eye and skin.
John Draize
helps predict a drug’s toxicity to humans.
In the early 1960s, thousands of babies were born with debilitating birth defects caused by ________. After this incident, all the regulatory agencies concentrated on determining the toxicity profiles of all pharmaceutical substances available for regular patient use and made mandatory the submission of toxicity profiles of investigational new drugs (IND).
Toxicity studies…
thalidomide
