Four Phases Of Pharmacokinetics

The drug is primarily administered to a patient orally and the majority of the dosage is rapidly absorbed in the GI tract. Once ingested and absorbed, metoprolol quickly disperses throughout the body. Approximately 10% of metoprolol in the blood binds to serum albumin. Metabolism of the drug in the body occurs through the combination of alpha-hydroxylation, O-demethylation, and N-dealkylation via oxidative deamination.

During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies.

The absorption of drugs differ in the elderly than they do in adults. Absorption primary occurs in the gastrointestinal system. The pH in the gastro intestinal system is higher because of the reduction in acid production in the stomach. Emptying is also decreased; this does not allow the drug to move on further into the system to be absorbed. Blood flow to the gastrointestinal system is reduced by 40-50% because of the decrease in cardiac output and decreased perfusion. The reduction of blood flow causes the villi in the stomach lining to become blunt and flattened. The reduction in blood flow and surface area results in the decreased absorption of drugs. (Lilley, Collins, and Snyder

Absorption – “How the drugs enter the circulation process through the body, and how they resist general breakdown by the stomach, liver, and the intestines”. Some of the factors that affect the absorption of drugs in the body is as follows, “acidity of the stomach, Physiochemical properties, Presence of food in the stomach or intestine, and Routes of administration”,

Patients walk into our clinics daily with a variety of complaints. Many things we can observe and assess drive our decisions for plans of care. However, there are some things about our patients we can’t see. Some things nobody would know under normal circumstances. How most medications are metabolized is predictable across the population, but some medications throw us a curve ball. Polypharmacy is a necessity in primary care. As primary care providers (PCPs) we see patients for both chronic and acute pathologies. Understanding metabolic pathways is expected of us as providers, but that doesn’t make us invulnerable to poor outcomes despite best efforts. In the following

During the absorption of Codeine by the GI tract, maximum plasma concentration can occur 60 minutes post of administration.

Based on ¨Principles of Pharmacokinetics¨, ¨pharmacokinetics is the study of absorption, distribution, metabolism, and excretion¨ (Ratain 2003). In other words, the drug's pharmacokinetics determines the duration and the intensity of the effect on the body. Absorption rate can be affected by the drug itself, such as: rate of dissolution, lipid solubility, and route (VandeWaa 2016). The absorption process starts by the route of admission, in this case oral. The oral, or by mouth, route of administration for drugs is the most common. When a pill is taken by mouth, it travels down to the stomach, were most pills dissolve. While in the stomach, some kinds of pills are absorbed into the stomach lining, but some move on to the small intestine. Every pill eventually ends up in the bloodstream and circulate through the body to tissues and organs (Howell 2017). Once passive diffusion occurs, the cells absorb the molecules of the medicine. Then, the molecules of the medicine will exit the cells and travel in the bloodstream for the distribution process.

The first step in developing a drug is pre-clinical testing. The experimental drug is tested in a laboratory and in animal studies. The drug has to meet safety standards and show potential for being a new drug. If this criterion is met, the drug moves on to the next phase. Phase 1 is concentrated on making sure the drug is safe to use on humans. This is the first time the experimental drug is used on people. Different measures of dosages of the drug are given to a small number of the volunteers. This allows the researchers to be able to measure the body’s response to the drug. The things they measure include how the drug is absorbed, its duration in the bloodstream, and what dosage levels are safe and well accepted by the body. If the experimental drug is deemed safe, it passes on to Phase 2 (Phases of Development, par. 6-7).

Pharmacokinetics (PK): Well absorbed in the gastrointestinal tract, metabolised in the liver and excreted in the urine. 1-2,4 The average PK parameters of DVS with once-daily dosing are1,4:

Much of what is recognized about the biological grounds of psychiatric disorders derives from pharmacological studies; pharmacology deals with all characteristics of the interaction of chemicals with biological systems, and psychopharmacology denotes to the interactions of drugs that are used predominantly because of their effects on the central nervous system (Kelsey et al., 2006). Pharmacologists characteristically distribute their science into two distinct portions; this would comprise of pharmacokinetics and pharmacodynamics. When defined in the humblest arrangement, pharmacokinetics endeavors to pronounce what the body does to the drug, and pharmacodynamics terms what the drug does to the body (Kelsey et al., 2006). In educations of mental illnesses, such as unipolar and bipolar mood disorders, pharmacodynamics discloses the molecular substrates of drugs that effect mental states, and henceforth molecular and cellular suppliers to these specific mental conditions.

absorption of acetaminophen has a pKa of 9.5 and in the alkaline medium of the duodenum

has a bioavailability that is linear until about 3mg at 40%. It then follows a nonlinear

As doses shift from low to high, the relative importance of individual enzymes involved in the metabolism may also shift. For example, at the high dose, oxon formation correlated best the CYP3A4 activity, while at the low dose, oxon formation correlated best with the higher affinity enzyme CYP2B6. Nutrition plays a role in metabolism(Croom, 2012). Poor nutrition limits the available energy for metabolism. Metabolizing enzymes require cofactors and micronutrients that may be lost with inadequate nutrition. Food itself can change the amount of xenobiotic available for metabolism by affecting its solubility, as well as by altering gastric emptying and bioavailability(Croom, 2012). Oral exposures involve first-pass metabolism, where the bulk of the blood collected from gastrointestinal tract first passes through the liver before being transported to the rest of the body(Croom, 2012). For xenobiotics with significant dermal absorption or significant exposure through inhalation, this can dramatically increase the amount available in the circulation and if the target organ is capable of bioactivation result in significant toxicity in that

Personalized drug dosing increases the efficacy and decreasing the risks of such adverse reactions. Traditional manufacturing processes are not suitable for making personalised medicines, and they tend to restrict the creation of dosage forms of complex geometries and drug profiles. These drugs are beneficial to the patients since pharmacists analyze patient 's profile such as race, gender and age to determine medication.

These drug metabolizing enzymes absorb and eliminate the drug through various routes of metabolic biotransformation. Phase I enzymes mainly catalyze the oxidation, reduction, and hydrolysis reactions, e.i. Cytochrome P450s (CYPs) are abundantly present in the liver and oxidize small molecules. Phase II enzymes catalyze mainly conjugation reactions that involve glucuronidation, sulfation, and acetylation. Lastly, hepatic transporters allow drugs to be absorbed and eliminated from the liver. Therefore, the biotransformation of drug in the body is important to factor to be considered.