Pharmacokinetics and drug disposition
Download as PPTX, PDF•10 likes•6,792 views
The document discusses pharmacokinetics, which encompasses the movement and alteration of drugs in the body, covering absorption, distribution, biotransformation, and excretion. It highlights critical concepts such as bioavailability, bioequivalence, and the roles of metabolism and excretion pathways like urine, feces, and breath. Additionally, the document outlines how factors like lipid solubility, plasma protein binding, and routes of administration affect drug kinetics.
Pharmacokinetics and drug disposition
- 1. PHARMACOKINETICS AND DRUG DISPOSITION SACHIN KUMAR B.SC. BIOTECH 6TH SEMESTER
- 2. PHARMACOKINETICS • Pharmacokinetics (Greek: Kinesis—movement) • This refers to movement of the drug in and alteration of the drug by the body; includes absorption, distribution, binding/ localization/ storage, biotransformation and excretion of the drug. • e.g. paracetamol is rapidly and almost completely absorbed orally attaining peak blood levels at 30–60 min; 25% bound to plasma proteins, widely and almost uniformly distributed in the body
- 3. ABSORPTION • Absorption is movement of the drug from its site of administration into the circulation. • Not only the fraction of the administered dose that gets absorbed, but also the rate of absorption is important. • The drug has to cross biological membranes; absorption is governed by: - • Concentration Passive diffusion depends on concentration gradient; drug given as concentrated solution is absorbed faster than from dilute solution.
- 4. • Aqueous solubility: Drugs given in solid form must dissolve in the aqueous biophase before they are absorbed. For poorly water soluble drugs (aspirin, griseofulvin) rate of dissolution governs rate of absorption. • Area of absorbing surface: Larger is the surface area, faster is the absorption. • Route of administration This affects drug absorption, because each route has its own peculiarities. Example oral, skin, muscular etc.
- 5. BIOAVAILABILITY • Bioavailability: is a subcategory of absorption. • Bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action determined by its concentration- time curve in blood or by its excretion in urine. • when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as orally), its bioavailability generally decreases (due to incomplete absorption.
- 6. BIOEQUIVALENCE • Oral formulations of a drug from different manufacturers or different batches from the same manufacturer may have the same amount of the drug (chemically equivalent) but may not yield the same blood levels—biologically inequivalent. • Two preparations of a drug are considered bioequivalent when the rate and extent of bioavailability of the active drug from them is not significantly different under suitable test conditions.
- 7. DISTRIBUTION • Once a drug has gained access to the blood stream, it gets distributed to other tissues that initially had no drug, concentration gradient. • Highly lipid-soluble drugs get initially distributed to organs with high blood flow, i.e. brain, heart, kidney, etc. Later, less vascular. • Greater the lipid solubility of the drug, faster is its redistribution.
- 8. DISTRIBUTION • Plasma protein binding: Most drugs possess physicochemical affinity for plasma proteins and get reversibly bound to these. • Acidic drugs generally bind to plasma albumin and basic drugs to α1 acid glycoprotein. • The bound drug fraction is not available for action. However, it is in equilibrium with the free drug in plasma and dissociates when the concentration of the latter is reduced due to elimination. Plasma protein binding thus a temporary storage of the drug. Thus tend to have longer duration of action.
- 9. BIOTRANSFORMATION (METABOLISM) • Chemical alteration of the drug in the body. • Compounds begin to break down as soon as they enter the body. • The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. • As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites.
- 10. BIOTRANSFORMATION (METABOLISM) Activation of inactive drug: • Few drugs are inactive as such and need conversion in the body to one or more active metabolites. Such a drug is called a prodrug. • Metabolic activation means that a less reactive compound is converted to a more reactive molecule. This usually occurs during Phase 1 reactions. • Phase 1 reaction refers to the first step in metabolism. It usually means that the compound is oxidized. Oxidation usually makes the compound more water soluble and facilitates further reactions.
- 11. BIOTRANSFORMATION (METABOLISM) Inactivation • Most drugs and their active metabolites are rendered inactive or less active, e.g. ibuprofen, paracetamol. • Metabolic inactivation means that an active or toxic molecule is converted to a less active metabolite. This usually occurs during Phase 2 reactions. • Phase 2 reaction refers to the second step in xenobiotic metabolism. It usually means that the oxidized compound is conjugated with (coupled to) an endogenous molecule. This reaction increases the water solubility further.
- 12. EXCRETION • Excretion is the exit of a substance and its biotransformation products from the organism. 1. Urine Through the kidney. It is the most important channel of excretion for majority of drugs. 2. Faeces Apart from the unabsorbed fraction, most of the drug present in faeces is derived from bile. 3. Elimination by exhaled air via lungs: Gases and vapours with low solubility in blood will be quickly eliminated this way.
- 13. EXCRETION 4. Sweat: Many non-electrolytes can be partially eliminated via skin by sweat: ethyl alcohol, acetone, phenols, carbon disulphide and chlorinated hydrocarbons. 5. Saliva: Some drugs and metallic ions can be excreted through the mucosa of the mouth by saliva
- 14. CLEARANCE (CL) • The clearance of a drug is the theoretical volume of plasma from which the drug is completely removed in unit time. • It can be calculated as CL = Rate of elimination/C where C is the plasma concentration.
- 15. Thank you