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ADME
- 1. ADME Presented by Md. AshfaqAziz ID: 1925486670 Course title: Pharmaceutical Biotechnology Course code: BBT 695 Department of Biochemistry and Microbiology North South University
- 2. Introduction ■ ADME isan abbreviation in pharmacokinetics and pharmacology for "absorption, distribution, metabolism, and excretion", and describes the disposition of a pharmaceutical compound within a body. ■ The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug.
- 3. Pharmacokinetics and Pharmacodynamics ■Pharmacokinetics: How the drug concentration change as it moves through the different compartments of our body. ■ Pharmacodynamics: How does the drug exert its effect on our body. ■ Pharmacokinetics is the study of how a body affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.
- 4. ADME The various compartmentsthat the model is divided into are commonly referred to as the ADME scheme: 1. Absorption – the process of a substance entering the blood circulation. 2. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. 3. Metabolism (or biotransformation, or inactivation) – the irreversible transformation of parent compounds into daughter metabolites. 4. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.
- 5. 1. Absorption ■ Fora drug compound to reach a tissue, it usually must be taken into the bloodstream - often via mucous surfaces like the digestive tract (intestinal absorption) - before being taken up by the target cells.
- 6. Routes of DrugAdministration Routes of Drug Administration Enteral Parenteral Topical Oral Sublingual Buccal Rectal Subcutaneous Intramuscular Intravenous Intradermal Eye Nose Ears Lungs Vagina Urethra Colon
- 7. Different Mechanism ofDrug Absorption • Passive transport – Diffusion • Simple diffusion • Facilitated diffusion – Osmosis: Aquaporins • Active transport – Energy is required for this process – Primary & secondary active transport mechanism • Vesicular transport – Endocytosis • Receptor mediated endocytosis • Phagocytosis • Bulk phase endocytosis (pinocytosis) – Exocytosis – Transcytosis: Placental circulation of antibody from mother to fetus
- 9. 2. Distribution ■ Thedrug compound needs to be carried to its effector site, most often via the bloodstream. From there, the compound may distribute into muscle and organs, usually to differing extents. After entry into the systemic circulation, either by intravascular injection or by absorption from any of the various extracellular sites, the drug is subjected to numerous distribution processes that tend to lower its plasma concentration.
- 10. Volume of Distribution(V) ■ Definition: Apparent Volume of distribution is defined as the volume that would accommodate all the drugs in the body, if the concentration was the same as in plasma. ■ Expressed as: in Liters Dose administered IV V = Plasma concentration
- 11. Transporters in PharmacokineticPathways
- 12. 3. Metabolism ■ Drugsbegin 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. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body. Metabolites may also be pharmacologically active, sometimes more so than the parent drug. ■ Factors Affecting Drug Metabolism: • Age • Disease • Species Differences • Heredity/ Genetics • Sex; Pregnancy • Environmental Factors • Drug Dose • Enzyme Induction • Enzyme Inhibition • Diet
- 13. Phases of DrugMetabolism Metabolism Phase I metabolism It produces more hydrophilic molecule to be easily removed from the body Phase II metabolism It makes the drug less lipid soluble and more easily excreted Oxidation Makes drug electrophilic Reduction Makes drug nucleophilic Hydrolysis Makes drug nucleophilic Glucuronide conjugation Acetylation Methylation Sulfate conjugation Glycine conjugation Glutathione conjugation Ribonucleoside/nucleotide synthesis
- 14. 4. Excretion ■ Drugsand their metabolites need to be removed from the body via excretion, usually through the kidneys (urine) or in the feces. Unless excretion is complete, accumulation of foreign substances can adversely affect normal metabolism. ■ There are three main sites where drug excretion occurs. -(1) The kidney is the most important site and it is where products are excreted through urine. -(2) Biliary excretion or fecal excretion is the process that initiates in the liver and passes through to the gut until the products are finally excreted along with waste products or feces. -(3) The last main method of excretion is through the lungs (e.g. anesthetic gases)
- 15. Mechanisms of Excretion ■Excretion of drugs by the kidney involves 3 main mechanisms: 1. Glomerular filtration of unbound drug. 2. Active secretion of (free & protein-bound) drug by transporters (e.g. anions such as urate, penicillin, glucuronide, sulfate conjugates) or cations such as choline, histamine. 3. Filtrate 100-fold concentrated in tubules for a favorable concentration gradient so that it may be secreted by passive diffusion and passed out through the urine.
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