Pharmacokinetic Aspects

Pharmacokinetic aspects Drugs that enter the body through various administration methods will generally experience absorption, distribution, metabolism, and binding at their place of action and cause effects. Pharmacokinetics is defined as every process that the body carries out on drugs, namely absorption, distribution, biotransformation (metabolism), distribution and excretion (ADME), so it is often also interpreted as the fate of drugs in the body. In a narrow sense, pharmacokinetics specifically studies changes in drug concentrations of drugs and their metabolites in and in tissues based on changes in time. In the human body, drugs must penetrate cell barriers in various tissues. In general, drugs cross the cell layers by penetrating them, not through the gaps between cells, except at the capillary endothelium. Cross-barrier transport is the most important event in the pharmacokinetic process. Two layers of fat which form a hyrophilic phase on both sides of the membrane and a hydrophobic phase on both sides of the membrane and a hydrophobic phase in between are concsist in the cell membrane. The most important ways of transporting drugs across membranes are passive diffusion and active transport. The shape and size of the molecule, solubility in water, degree of ionization and solubility in at are some process that determine by rhe physico-chemical properties of drugs. 1. Absorption and Bioavailability Absorption describes the rate at which the drug leaves the site of administration and the amount. However, the more important parameter is bioavailability, rather than absorption. The fraction of a drug does that reaches its site of action or the body fluids that the drugs passes through before reaching its site of action is called bioavailability. This kind of condition can found in an example like the drugs drugs given orally must first be absorbed from the stomach and intestines but this is limited by the characteristics of the drug dosage form/or the physicochemical properties of the drug. Next, the drug will pass through the liver where metabolism and/or biliary excretion can occur before the drug reaches the systemic circulation. Thus, a number of fractions of the drug dose administered and absorbed will undergo inactivation or decomposition before the drug reaches the blood circulation and is distributed to its site of action. If the metabolic and excretory capacities of the liver for the drug are large, the bioavailability of the drug will be significantly reduced (this is called the first-pass effect). The decrease in bioavailability is influenced by anatomical, physiological and other pathological factors. Apart from that, the route of drug administration must also be based on an understanding of the condition. 2. Distribution After the drug is absorbed or the drug is administered systemically into the blood, a drug will be distributed into the interstitial fluid and intracellular fluid. This process involves a number of physiological factors, especially the physicochemical properties of each drug. Important factors related to drug distribution include a. Perfusion of blood through tissues Blood perfusion through tissues and organs varies widely. High perfusion is in the lungs, liver, kidneys, heart, brain and areas with low perfusion are fat and bones. Meanwhile, perfusion to muscles and skin is moderate. Changes in blood flow velocity (heart disease) will change the perfusion of organs such as the liver and kidneys and affect the speed of drug elimination. b. Gradient levels, pH and substance bonds with macromolecules Drug penetration depends on the extent of the gradient, the form that can diffuse freely, factors such as the pH gradient and binding to intracellular constituents will influence accumulation in tissues. c. Partition into fat Lipid-soluble drugs can reach high concentrations in fatty tissue. The drug will be stored by physical solution in neutral fat. The amount of fat is 15% of body weight and is a storage place for drugs. There are fats too role in limiting the effects of compounds whose solubility in fat is high by working as drug acceptors during the redistribution phase. d. Active transport Entry into the network can also occur by active transport processes. Methadone, propranolol and amphetamine are transported into the lung tissue by active processes. This is an important mechanism for large drug entry into the lungs. e. Sawar Drug distribution to the central nervous system and fetus must penetrate special barriers, namely the blood brain barrier and the urinary barrier. Bloodbrain barrier, drug penetration from the bloodstream into the extracellular space of the central nervous system and cerebrospinal fluid is limited or determined by the state of the absorption surface. f. Drug binding to plasma proteins An important factor in drug distribution is its binding to plasma proteins which are macromolecules. Many drugs are bound to proteins in blood plasma and other tissues. Generally, binding is a reversible process and will affect drug availability.