SD - Basic Pharmacokinetics-2 B26-1.pdf

Drug Absorption Absorption is movement of the drug from its site of administration into the circulation. ▪ If oral……from Stomach & Intestine to circulation ▪ If Per-rectal……from Rectum to circulation ▪ If Intramuscular…..from muscles to circulation et No absorption is needed if given Intravenously...

Drug Absorption Absorption is movement of the drug from its site of administration into the circulation. ▪ If oral……from Stomach & Intestine to circulation ▪ If Per-rectal……from Rectum to circulation ▪ If Intramuscular…..from muscles to circulation et No absorption is needed if given Intravenously • Cell Membrane Processes of Drugs absorption ▪ Passive or simple diffusion ▪ Facilitated diffusion ▪ Active transport ▪ Endocytosis and exocytosis Simple or Passive diffusion process: The passage of drug molecule from one compartment to another compartment along its concentration gradient through the membrane without the necessity of binding with carrier protein. Almost all drugs are absorbed by simple passive diffusion with exception of a few Facilitated Transport ▪ A type of passive transport. ▪ Carrier-mediated transport. ▪ Materials diffuse across the plasma membrane with the help of membrane proteins Eg- Absorption of Vitamin B12 from the gut, Uptake of glucose by cell Active Transport ▪ Drugs molecule pass across biological membrane against their concentration gradient ▪ with the help of carriers ▪ with expenditure of energy. Site of active transport: Neuronal membrane &BBB, Choroid plexus,Renal tubular cell, Biliary Tract, GIT Examples: Iron and levodopa absorption Endocytosis ▪ When membrane engulfs drug molecule by making a pseudopod is called endocytosis. ▪ Specific receptors for the transport proteins must be present for this process to work e.g., the transport of vitamin B12 across the wall of the gut into the blood. Exocytosis Transport of neurotransmitter substances from presynaptic nerve endings into the extracellular space. First-pass metabolism/pre-systemic elimination Metabolism of a drug during its passage from the site of absorption into the systemic circulation is called first-pass metabolism or pre-systemic elimination By Oral route – drug may undergo metabolism in intestine, portal circulation & liver (predominantly) before entering into systemic circulation. Drugs with high first pass metabolism Propranolol, lidocaine, Nitroglycerine, Salbutamol ▪ IV administration, which confers 100% bioavailability. ▪ Orally administered drugs often undergo first-pass metabolism (B < 100%). Factors affecting oral drug absorption and bioavailability A. Drug related factors by oral route a) Physical state b) Lipid and water solubility c) Particle size d) Disintegration time and dissolution rate ↑Disintegration time and dissolution rate →↓ rate of Absorption e) Formulation - tetracycline with calcium or magnesium as excipients retard the absorption and Bioavailability Factors affecting oral drug absorption and bioavailability (f) Ionization constant and Effect of pKa • Non-ionized forms are lipid soluble & diffuse across the membrane, hence easily absorbed • Ionized forms are lipid insoluble, water soluble & can not cross the membrane, hence poorly absorbed • Concentration of ionized and non-ionized form of a drug is determined by pH of the medium and pKa of a drug • pKa – is the pH at which half (50%) the drug is in its ionized form • pKa usually Low for Acidic drugs & High for Basic drugs Factors affecting oral drug absorption and bioavailability (B) Patients related factors by oral route a)Surface area b)Motility of GIT : Drugs are better absorbed in normal GIT movement c) Blood supply at the absorptive area (d) Presence of food • More absorption in empty stomach • Antacid prevents absorption of Tetracycline • Milk (Ca) - can reduce tetracycline absorption • Food – reduce the absorption of ampicillin, • Fatty diets - ↑the absorption of griseofulvin Patients related factors by oral route e) Gastric emptying time ↑gastric emptying time → ↓ rate of absorption food & Drugs Metoclopramide increases gastric motility and accelerates gastric emptying and hence aid in rapid absorption While fatty meal, antimotility drugs (Atropine), exercise & stress can slow gastric emptying and delay the rate of absorption and onset of action f) Destruction of drug in GIT • Benzyl penicillin is destroyed by gastric HCL • Insulin is destroyed by proteolytic enzymes