European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
Food and Drug Administration
The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements and over-the-counter pharmaceutical drugs, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, animal foods & feed and veterinary products; as of 2017, 3/4th of the FDA budget is paid by people who consume pharmaceutical products, due to the Prescription Drug User Fee Act. The FDA was empowered by the United States Congress to enforce the Federal Food and Cosmetic Act, which serves as the primary focus for the Agency; these include regulating lasers, cellular phones and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate.
The Commissioner reports to the Secretary of Human Services. Scott Gottlieb, M. D. is the current commissioner, who took over in May 2017. The FDA has its headquarters in Maryland; the agency has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, Puerto Rico. In 2008, the FDA began to post employees to foreign countries, including China, Costa Rica, Chile and the United Kingdom. In recent years, the agency began undertaking a large-scale effort to consolidate its 25 operations in the Washington metropolitan area, moving from its main headquarters in Rockville and several fragmented office buildings to the former site of the Naval Ordnance Laboratory in the White Oak area of Silver Spring, Maryland; the site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the naval facility was kept.
All other buildings are new construction. The project is slated to be completed by 2021, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. area as part of the Headquarters divisions, two offices – the Office of Regulatory Affairs and the Office of Criminal Investigations – are field offices with a workforce spread across the country. The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field. Consumer Safety Officers, more called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, review documentation in the case of medical devices, biological products, other items where it may be difficult to conduct a physical examination or take a physical sample of the product; the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based on the geographic divisions of the federal court system.
Each district comprises a main district office and a number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA includes the Agency's network of regulatory laboratories, which analyze any physical samples taken. Though samples are food-related, some laboratories are equipped to analyze drugs and radiation-emitting devices; the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, don't focus on technical aspects of the regulated industries. OCI agents pursue and develop cases where individuals and companies have committed criminal actions, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving Title 18 violations, in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents come from other criminal investigations backgrounds, work with the Federal Bureau of Investigation, Assistant Attorney General, Interpol.
OCI receives cases from a variety of sources—including ORA, local agencies, the FBI—and works with ORA Investigators to help develop the technical and science-based aspects of a case. OCI is a smaller branch; the FDA works with other federal agencies, including the Department of Agriculture, Drug Enforcement Administration and Border Protection, Consumer Product Safety Commission. Local and state government agencies work with the FDA to provide regulatory inspections and enforcement action; the FDA regulates more than US$2.4 trillion worth of consumer goods, about 25% of consumer expenditures in the United States. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. Much of these expenditures are for goods imported into the United States; the FDA's federal budget request for fiscal year 2012 totaled $4.36 billion, while the proposed 2014 budget is $4.7 billion. About $2 billion of this budget is generated by user fees.
Pharmaceutical firms pay th
Europe is a continent located in the Northern Hemisphere and in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west and the Mediterranean Sea to the south, it comprises the westernmost part of Eurasia. Since around 1850, Europe is most considered to be separated from Asia by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas and the waterways of the Turkish Straits. Although the term "continent" implies physical geography, the land border is somewhat arbitrary and has been redefined several times since its first conception in classical antiquity; the division of Eurasia into two continents reflects East-West cultural and ethnic differences which vary on a spectrum rather than with a sharp dividing line. The geographic border does not follow political boundaries, with Turkey and Kazakhstan being transcontinental countries. A strict application of the Caucasus Mountains boundary places two comparatively small countries and Georgia, in both continents.
Europe covers 2 % of the Earth's surface. Politically, Europe is divided into about fifty sovereign states of which the Russian Federation is the largest and most populous, spanning 39% of the continent and comprising 15% of its population. Europe had a total population of about 741 million as of 2016; the European climate is affected by warm Atlantic currents that temper winters and summers on much of the continent at latitudes along which the climate in Asia and North America is severe. Further from the sea, seasonal differences are more noticeable than close to the coast. Europe, in particular ancient Greece, was the birthplace of Western civilization; the fall of the Western Roman Empire in 476 AD and the subsequent Migration Period marked the end of ancient history and the beginning of the Middle Ages. Renaissance humanism, exploration and science led to the modern era. Since the Age of Discovery started by Portugal and Spain, Europe played a predominant role in global affairs. Between the 16th and 20th centuries, European powers controlled at various times the Americas all of Africa and Oceania and the majority of Asia.
The Age of Enlightenment, the subsequent French Revolution and the Napoleonic Wars shaped the continent culturally and economically from the end of the 17th century until the first half of the 19th century. The Industrial Revolution, which began in Great Britain at the end of the 18th century, gave rise to radical economic and social change in Western Europe and the wider world. Both world wars took place for the most part in Europe, contributing to a decline in Western European dominance in world affairs by the mid-20th century as the Soviet Union and the United States took prominence. During the Cold War, Europe was divided along the Iron Curtain between NATO in the West and the Warsaw Pact in the East, until the revolutions of 1989 and fall of the Berlin Wall. In 1949 the Council of Europe was founded, following a speech by Sir Winston Churchill, with the idea of unifying Europe to achieve common goals, it includes all European states except for Belarus and Vatican City. Further European integration by some states led to the formation of the European Union, a separate political entity that lies between a confederation and a federation.
The EU originated in Western Europe but has been expanding eastward since the fall of the Soviet Union in 1991. The currency of most countries of the European Union, the euro, is the most used among Europeans. In classical Greek mythology, Europa was a Phoenician princess; the word Europe is derived from her name. The name contains the elements εὐρύς, "wide, broad" and ὤψ "eye, countenance", hence their composite Eurṓpē would mean "wide-gazing" or "broad of aspect". Broad has been an epithet of Earth herself in the reconstructed Proto-Indo-European religion and the poetry devoted to it. There have been attempts to connect Eurṓpē to a Semitic term for "west", this being either Akkadian erebu meaning "to go down, set" or Phoenician'ereb "evening, west", at the origin of Arabic Maghreb and Hebrew ma'arav. Michael A. Barry, professor in Princeton University's Near Eastern Studies Department, finds the mention of the word Ereb on an Assyrian stele with the meaning of "night, sunset", in opposition to Asu " sunrise", i.e. Asia.
The same naming motive according to "cartographic convention" appears in Greek Ἀνατολή. Martin Litchfield West stated that "phonologically, the match between Europa's name and any form of the Semitic word is poor." Next to these hypotheses there is a Proto-Indo-European root *h1regʷos, meaning "darkness", which produced Greek Erebus. Most major world languages use words derived from Europa to refer to the continent. Chinese, for example, uses the word Ōuzhōu. In some Turkic languages the Persian name Frangistan is used casually in referring to much of Europe, besides official names such as Avrupa or Evropa; the prevalent definition of Europe as a geographical term has been in use since the mid-19th century. Europe is taken to be bounded by large bodies of water
The modern Olympic Games or Olympics are leading international sporting events featuring summer and winter sports competitions in which thousands of athletes from around the world participate in a variety of competitions. The Olympic Games are considered the world's foremost sports competition with more than 200 nations participating; the Olympic Games are held every four years, with the Summer and Winter Games alternating by occurring every four years but two years apart. Their creation was inspired by the ancient Olympic Games, which were held in Olympia, from the 8th century BC to the 4th century AD. Baron Pierre de Coubertin founded the International Olympic Committee in 1894, leading to the first modern Games in Athens in 1896; the IOC is the governing body of the Olympic Movement, with the Olympic Charter defining its structure and authority. The evolution of the Olympic Movement during the 20th and 21st centuries has resulted in several changes to the Olympic Games; some of these adjustments include the creation of the Winter Olympic Games for snow and ice sports, the Paralympic Games for athletes with a disability, the Youth Olympic Games for athletes aged 14 to 18, the five Continental games, the World Games for sports that are not contested in the Olympic Games.
The Deaflympics and Special Olympics are endorsed by the IOC. The IOC has had to adapt to a variety of economic and technological advancements; the abuse of amateur rules by the Eastern Bloc nations prompted the IOC to shift away from pure amateurism, as envisioned by Coubertin, to allowing participation of professional athletes. The growing importance of mass media created the issue of corporate sponsorship and commercialisation of the Games. World wars led to the cancellation of the 1916, 1940, 1944 Games. Large boycotts during the Cold War limited participation in the 1980 and 1984 Games; the Olympic Movement consists of international sports federations, National Olympic Committees, organising committees for each specific Olympic Games. As the decision-making body, the IOC is responsible for choosing the host city for each Games, organises and funds the Games according to the Olympic Charter; the IOC determines the Olympic programme, consisting of the sports to be contested at the Games. There are several Olympic rituals and symbols, such as the Olympic flag and torch, as well as the opening and closing ceremonies.
Over 13,000 athletes compete at the Summer and Winter Olympic Games in 33 different sports and nearly 400 events. The first and third-place finishers in each event receive Olympic medals: gold and bronze, respectively; the Games have grown so much. This growth has created numerous challenges and controversies, including boycotts, bribery, a terrorist attack in 1972; every two years the Olympics and its media exposure provide athletes with the chance to attain national and sometimes international fame. The Games constitute an opportunity for the host city and country to showcase themselves to the world; the Ancient Olympic Games were religious and athletic festivals held every four years at the sanctuary of Zeus in Olympia, Greece. Competition was among representatives of several kingdoms of Ancient Greece; these Games featured athletic but combat sports such as wrestling and the pankration and chariot racing events. It has been written that during the Games, all conflicts among the participating city-states were postponed until the Games were finished.
This cessation of hostilities was known as truce. This idea is a modern myth; the truce did allow those religious pilgrims who were travelling to Olympia to pass through warring territories unmolested because they were protected by Zeus. The origin of the Olympics is shrouded in legend. According to legend, it was Heracles who first called the Games "Olympic" and established the custom of holding them every four years; the myth continues that after Heracles completed his twelve labours, he built the Olympic Stadium as an honour to Zeus. Following its completion, he walked in a straight line for 200 steps and called this distance a "stadion", which became a unit of distance; the most accepted inception date for the Ancient Olympics is 776 BC. The Ancient Games featured running events, a pentathlon, wrestling and equestrian events. Tradition has it that a cook from the city of Elis, was the first Olympic champion; the Olympics were of fundamental religious importance, featuring sporting events alongside ritual sacrifices honouring both Zeus and Pelops, divine hero and mythical king of Olympia.
Pelops was famous for his chariot race with King Oenomaus of Pisatis. The winners of the events were immortalised in poems and statues; the Games were held every four years, this period, known as an Olympiad, was used by Greeks as one of their units of time measurement. The Games were part of a cycle known as the Panhellenic Games, which included the Pythian Games, the Nemean Games, the Isthmian Games; the Olympic Games reached their zenith in the 6th and 5th centuries BC, but gradually declined in importance as the Romans gained power and influence in Gr
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
The thorax or chest is a part of the anatomy of humans and various other animals located between the neck and the abdomen. The thorax includes the thoracic wall, it contains organs including the heart and thymus gland, as well as muscles and various other internal structures. Many diseases may affect the chest, one of the most common symptoms is chest pain. In humans and other hominids, the thorax is the chest region of the body between the neck and the abdomen, along with its internal organs and other contents, it is protected and supported by the rib cage and shoulder girdle. The contents of the thorax include lungs. Arteries and veins are contained –. External structures are nipples. In the human body, the region of the thorax between the neck and diaphragm in the front of the body is called the chest; the corresponding area in an animal can be referred to as the chest. The shape of the chest does not correspond to that part of the thoracic skeleton that encloses the heart and lungs. All the breadth of the shoulders is due to the shoulder girdle, contains the axillae and the heads of the humeri.
In the middle line the suprasternal notch is seen above, while about three fingers' breadth below it a transverse ridge can be felt, known as the sternal angle and this marks the junction between the manubrium and body of the sternum. Level with this line the second ribs join the sternum, when these are found the lower ribs can be counted. At the lower part of the sternum, where the seventh or last true ribs join it, the ensiform cartilage begins, above this there is a depression known as the pit of the stomach; the bones of the thorax, called the "thoracic skeleton" is a component of the axial skeleton. It consists of sternum; the ribs of the thorax are numbered in ascending order from 1-12. 11 & 12 are known as floating ribs because they have no anterior attachment point in particular the cartilage attached to the sternum, as 1-7 are, therefore are termed "floating". Whereas ribs 8-10 are termed false ribs as their costal cartilage articulates with the costal cartilage of the rib above; the anatomy of the chest can be described through the use of anatomical landmarks.
The nipple in the male is situated in front of the fourth rib or a little below. A little below it the lower limit of the great pectoral muscle is seen running upward and outward to the axilla; the female nipple is surrounded for half an inch by the areola. The apex of a normal heart is in the fifth left intercostal space, three and a half inches from the mid-line. Different types of diseases or conditions that affect the chest include pleurisy, flail chest and the most common condition, chest pain; these conditions can be caused by birth defects or trauma. Any condition that lowers the ability to either breathe or to cough is considered a chest disease or condition. Injury to the chest results in up to ¼ of all deaths due to trauma in the United States; the major pathophysiologies encountered in blunt chest trauma involve derangements in the flow of air, blood, or both in combination. Sepsis due to leakage of alimentary tract contents, as in esophageal perforations must be considered. Blunt trauma results in chest wall injuries.
The pain associated with these injuries can make breathing difficult, this may compromise ventilation. Direct lung injuries, such as pulmonary contusions, are associated with major chest trauma and may impair ventilation by a similar mechanism. Chest pain can be the result of multiple issues, including respiratory problems, digestive issues, musculoskeletal complications; the pain can trigger cardiac issues as well. Not all pain, felt is associated with the heart, but it should not be taken either. Symptoms can be different depending on the cause of the pain. While cardiac issues cause feelings of sudden pressure in the chest or a crushing pain in the back and arms, pain, felt due to noncardiac issues gives a burning feeling along the digestive tract or pain when deep breaths are attempted. Different people feel pains differently for the same condition. Only a patient knows if the symptoms are mild or serious. Chest pain may be a symptom of myocardial infarctions. If this condition is present in the body, discomfort will be felt in the chest, similar to a heavy weight placed on the body.
Sweating, shortness of breath and irregular heartbeat may be experienced. If a heart attack occurs, the bulk of the damage is caused during the first six hours, so getting the proper treatment as as possible is important; some people those who are elderly or have diabetes, may not have typical chest pain but may have many of
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s