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
Japan is an island country in East Asia. Located in the Pacific Ocean, it lies off the eastern coast of the Asian continent and stretches from the Sea of Okhotsk in the north to the East China Sea and the Philippine Sea in the south; the kanji that make up Japan's name mean "sun origin", it is called the "Land of the Rising Sun". Japan is a stratovolcanic archipelago consisting of about 6,852 islands; the four largest are Honshu, Hokkaido and Shikoku, which make up about ninety-seven percent of Japan's land area and are referred to as home islands. The country is divided into 47 prefectures in eight regions, with Hokkaido being the northernmost prefecture and Okinawa being the southernmost one; the population of 127 million is the world's tenth largest. 90.7 % of people live in cities. About 13.8 million people live in the capital of Japan. The Greater Tokyo Area is the most populous metropolitan area in the world with over 38 million people. Archaeological research indicates; the first written mention of Japan is in Chinese history texts from the 1st century AD.
Influence from other regions China, followed by periods of isolation from Western Europe, has characterized Japan's history. From the 12th century until 1868, Japan was ruled by successive feudal military shōguns who ruled in the name of the Emperor. Japan entered into a long period of isolation in the early 17th century, ended in 1853 when a United States fleet pressured Japan to open to the West. After nearly two decades of internal conflict and insurrection, the Imperial Court regained its political power in 1868 through the help of several clans from Chōshū and Satsuma – and the Empire of Japan was established. In the late 19th and early 20th centuries, victories in the First Sino-Japanese War, the Russo-Japanese War and World War I allowed Japan to expand its empire during a period of increasing militarism; the Second Sino-Japanese War of 1937 expanded into part of World War II in 1941, which came to an end in 1945 following the Japanese surrender. Since adopting its revised constitution on May 3, 1947, during the occupation led by SCAP, the sovereign state of Japan has maintained a unitary parliamentary constitutional monarchy with an Emperor and an elected legislature called the National Diet.
Japan is a member of the ASEAN Plus mechanism, UN, the OECD, the G7, the G8, the G20, is considered a great power. Its economy is the world's third-largest by nominal GDP and the fourth-largest by purchasing power parity, it is the world's fourth-largest exporter and fourth-largest importer. Japan benefits from a skilled and educated workforce. Although it has renounced its right to declare war, Japan maintains a modern military with the world's eighth-largest military budget, used for self-defense and peacekeeping roles. Japan is a developed country with a high standard of living and Human Development Index, its population enjoys the highest life expectancy and third lowest infant mortality rate in the world, but is experiencing issues due to an aging population and low birthrate. Japan is renowned for its historical and extensive cinema, influential music industry, video gaming, rich cuisine and its major contributions to science and modern technology; the Japanese word for Japan is 日本, pronounced Nihon or Nippon and means "the origin of the sun".
The character nichi means "sun" or "day". The compound therefore means "origin of the sun" and is the source of the popular Western epithet "Land of the Rising Sun"; the earliest record of the name Nihon appears in the Chinese historical records of the Tang dynasty, the Old Book of Tang. At the end of the seventh century, a delegation from Japan requested that Nihon be used as the name of their country; this name may have its origin in a letter sent in 607 and recorded in the official history of the Sui dynasty. Prince Shōtoku, the Regent of Japan, sent a mission to China with a letter in which he called himself "the Emperor of the Land where the Sun rises"; the message said: "Here, I, the emperor of the country where the sun rises, send a letter to the emperor of the country where the sun sets. How are you". Prior to the adoption of Nihon, other terms such as Yamato and Wakoku were used; the term Wa is a homophone of Wo 倭, used by the Chinese as a designation for the Japanese as early as the third century Three Kingdoms period.
Another form of Wa, Wei in Chinese) was used for an early state in Japan called Nakoku during the Han dynasty. However, the Japanese disliked some connotation of Wa 倭, it was therefore replaced with the substitute character Wa, meaning "togetherness, harmony"; the English word Japan derives from the historical Chinese pronunciation of 日本. The Old Mandarin or early Wu Chinese pronunciation of Japan was recorded by Marco Polo as Cipangu. In modern Shanghainese, a Wu dialect, the pronunciation of characters 日本; the old Malay word for Japan, Japun or Japang, was borrowed from a southern coastal Chinese dialect Fukienese or Ningpo – and this Malay word was encountered by Portuguese traders in Southeast Asia in the 16th century. These Early Portuguese traders brought the word
A tablet is a pharmaceutical dosage form. Tablets may be defined as the solid unit dosage form of medicament or medicaments with or without suitable excipients and prepared either by molding or by compression, it comprises a mixture of active substances and excipients in powder form, pressed or compacted from a powder into a solid dose. The excipients can include diluents, binders or granulating agents and lubricants to ensure efficient tabletting. A polymer coating is applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment, or to enhance the tablet's appearance; the compressed tablet is the most popular dosage form in use today. About two-thirds of all prescriptions are dispensed as solid dosage forms, half of these are compressed tablets. A tablet can be formulated to deliver an accurate dosage to a specific site; the tablet is just one of the many forms that an oral drug can take such as syrups, elixirs and emulsions.
Medicinal tablets were made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help distinguish different medicines. Tablets are stamped with symbols and numbers, which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Pills are thought to date back to around 1500 BC. Earlier medical recipes, such as those from 4000 BC, were for liquid preparations rather than solids; the first references to pills were found on papyruses in ancient Egypt, contained bread dough, honey or grease. Medicinal ingredients, such as plant powders or spices, were mixed in and formed by hand to make little balls, or pills. In ancient Greece, such medicines were known as katapotia, the Roman scholar Pliny, who lived from 23-79 AD, first gave a name to what we now call pills, calling them pilula. Pills have always been difficult to swallow and efforts long have been made to make them go down easier.
In medieval times, people coated pills with slippery plant substances. Another approach, used as as the 19th century, was to gild them in gold and silver, although this meant that they would pass through the digestive tract with no effect. In the 1800s sugar-coating and gelatin-coating was invented. In 1843, the British painter and inventor William Brockedon was granted a patent for a machine capable of "Shaping Pills and Black Lead by Pressure in Dies"; the device was capable of compressing powder into a tablet without use of an adhesive. A pill was defined as a small, solid pharmaceutical oral dosage form of medication; the oldest known pills were made of the zinc carbonates smithsonite. The pills were used for sore eyes, were found aboard a Roman ship Relitto del Pozzino which wrecked in 140 BC. Today, pills include tablets and variants thereof like caplets — any solid form of medication colloquially falls into the pill category. A caplet is a smooth, oval-shaped medicinal tablet in the general shape of a capsule.
Many caplets have an indentation running down the middle. Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication. For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the “caplet”, a portmanteau of “capsule-shaped tablet”, in order to tie this positive association to more efficiently-produced tablet pills, as well as being an easier-to-swallow shape than the usual disk-shaped tablet. An orally disintegrating tablet or orodispersible tablet, is a drug dosage form available for a limited range of over-the-counter and prescription medications. In the tablet-pressing process, it is important that all ingredients be dry, powdered or granular, somewhat uniform in particle size, flowing. Mixed particle sized powders segregate during manufacturing operations due to different densities, which can result in tablets with poor drug or active pharmaceutical ingredient content uniformity, but granulation should prevent this.
Content uniformity ensures. Some APIs may be tableted as pure substances, but this is the case. A pharmacologically inactive ingredient termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, corn starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose. An ingredient is needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption; some binders, such as starch and cellulose, are excellent disintegrants. Tablets are convenient to use, they provide an measured dosage of the active ingredient in a convenient portable package, can be designed to protect unstable medications or disguise unpalatable ingredients. Colored coatings, embossed markings and printing can be used to aid tablet recognition. Manufacturing processes and techniques can provid
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
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, poison, or other substance is taken into the body. Routes of administration are classified by the location at which the substance is applied. Common examples include intravenous administration. Routes can be classified based on where the target of action is. Action may be enteral, or parenteral. Route of administration and dosage form are aspects of drug delivery. Routes of administration are classified by application location; the route or course the active substance takes from application location to the location where it has its target effect is rather a matter of pharmacokinetics. Exceptions include the transdermal or transmucosal routes, which are still referred to as routes of administration; the location of the target effect of active substances are rather a matter of pharmacodynamics. An exception is topical administration, which means that both the application location and the effect thereof is local. Topical administration is sometimes defined as both a local application location and local pharmacodynamic effect, sometimes as a local application location regardless of location of the effects.
Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration. Enteral/enteric administration includes oral and rectal administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may occur in the stomach, as such gastrointestinal may be a more fitting term for this route of administration. Furthermore, some application locations classified as enteral, such as sublingual and sublabial or buccal, are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Enteral administration can be used for systemic administration, as well as local, such as in a contrast enema, whereby contrast media is infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects. Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy.
Substances may be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach; the rectal route is an effective route of administration for many medications those used at the end of life. The walls of the rectum absorb many medications and effectively. Medications delivered to the distal one-third of the rectum at least avoid the "first pass effect" through the liver, which allows for greater bio-availability of many medications than that of the oral route. Rectal mucosa is vascularized tissue that allows for rapid and effective absorption of medications. A suppository is a solid dosage form. In hospice care, a specialized rectal catheter, designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the distal rectum, giving health practitioners a way to leverage the established benefits of rectal administration.
The parenteral route is any route, not enteral. Parenteral administration can be performed by injection, that is, using a needle and a syringe, or by the insertion of an indwelling catheter. Locations of application of parenteral administration include: central nervous systemepidural, e.g. epidural anesthesia intracerebral direct injection into the brain. Used in experimental research of chemicals and as a treatment for malignancies of the brain; the intracerebral route can interrupt the blood brain barrier from holding up against subsequent routes. Intracerebroventricular administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain. Epicutaneous, it can be used both for local effect as in allergy testing and typical local anesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route. Sublingual and buccal medication administration is a way of giving someone medicine orally.
Sublingual administration is. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the cheek. These medications can come in the form of films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, barbiturates, opioid analgesics with poor gastrointestinal bioavailability and vitamins and minerals. Extra-amniotic administration, between the endometrium and fetal membranes nasal administration (th
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
Excretion is a process by which metabolic waste is eliminated from an organism. In vertebrates this is carried out by the lungs and skin; this is in contrast with secretion, where the substance may have specific tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in mammals urine is expelled through the urethra, part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell. During life activities such as cellular respiration, several chemical reactions take place in the body; these are known as metabolism. These chemical reactions produce waste products such as carbon dioxide, salts and uric acid. Accumulation of these wastes beyond a level inside the body is harmful to the body; the excretory organs remove these wastes. This process of removal of metabolic waste from the body is known as excretion. Green plants produce carbon water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis.
Oxygen is a by product generated during photosynthesis, exits through stomata, root cell walls, other routes. Plants can get rid of excess water by guttation, it has been shown that the leaf acts as an'excretophore' and, in addition to being a primary organ of photosynthesis, is used as a method of excreting toxic wastes via diffusion. Other waste materials that are exuded by some plants — resin, latex, etc. are forced from the interior of the plant by hydrostatic pressures inside the plant and by absorptive forces of plant cells. These latter processes do not need added energy, they act passively. However, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants excrete some waste substances into the soil around them. In animals, the main excretory products are carbon dioxide, urea, uric acid and creatine; the liver and kidneys clear many substances from the blood, the cleared substances are excreted from the body in the urine and feces. Aquatic animals excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution.
In terrestrial animals ammonia-like compounds are converted into other nitrogenous materials as there is less water in the environment and ammonia itself is toxic. Birds excrete their nitrogenous wastes as uric acid in the form of a paste. Although this process is metabolically more expensive, it allows more efficient water retention and it can be stored more in the egg. Many avian species seabirds, can excrete salt via specialized nasal salt glands, the saline solution leaving through nostrils in the beak. In insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is transported into the tubule, which transports the wastes to the intestines; the metabolic waste is released from the body along with fecal matter. The excreted material may be called ejecta. In pathology the word ejecta is more used. UAlberta.ca, Animation of excretion Brian J Ford on leaf fall in Nature