Biopharmaceutics 2022 Ally PDF

Why Biopharmaceutics? I Switched from Brand B to Brand C, but did not get the same effect? How do we compare 2 dosage forms ? What is the difference between these two? Discuss the various factors that influence oral drug absorption Describe drug distribution and drug elimination  Goal of a...

Why Biopharmaceutics? I Switched from Brand B to Brand C, but did not get the same effect? How do we compare 2 dosage forms ? What is the difference between these two? Discuss the various factors that influence oral drug absorption Describe drug distribution and drug elimination  Goal of a formulation / Medicine  Drug should come out of a formulation (dissolution)  It should get absorbed (Absorption)  Reach the site of action (Distribution)  Elicit its intended affect (Response)  Eliminate from the body (Metabolism & Excretion)  Bioavailability Def (US-FDA): the rate and extent at which the active drug is absorbed and becomes available at the site of action Routes of Drug Administration Blood / Plasma is the central compartment Concentration in the plasma reflects the extent and duration of the action Bioavailability –Measurable Parameters the rate and the extent of the administered dose reaching the systemic circulation (blood circulation) How fast / How long ? ka; Absorption rate k; Elimination rate tmax How much ? Cmax AUC for i.v.: 100% for non i.v.: ranges from 0 to 100% e.g. lidocaine bioavailability 35% due to destruction in gastric acid and liver metabolism  Comparing 2 dosage forms Bioequivalence- compares the bioavailability between different products for the same dose of same drug Compares rate and extent (should be within 80-120% of standard or innovator product)  Comparing 2 dosage forms-continue Bioequivalence- compares the bioavailability between different products for the same dose of same drug may be equivalent in the extent of their absorption but not in their rate of absorption and yet may be considered bioequivalent. This may be intentional- reflected on labeling,  Terminology Biopharmaceutics (body’s influence on drug liberation & absorption) Physico-chemical properties – drug absorption Pharmacokinetics Rate of ADME Pharmacodynamics Biochemical and pharmacological effects- MOA Terminology- continue LADMER PK is ADME  Physicochemical Properties- LADMER Liberation Dissolution Solubility, pKa , Diffusion coefficient, rate constant Absorption Solubility, Log P, pKa, MW, dissolution rate Distribution Log P, pKa, Solubility, MW, Chemical structure Metabolism Log P, MW, pKa, Functional groups Excretion Log P, MW, pKa, Functional groups, Solubility Response Log P, Conformation & Functional groups  Terminology-summary Biopharmaceutics Physico-chemical properties – drug absorption Pharmacokinetics Rate of ADME Pharmacodynamics Biochemical and pharmacological effects- MOA Bioavailability the rate and the extent of the administered dose reaching the systemic circulation Bioequivalence compares the bioavailability between different products for the same dose and same drug  DRUG ABSORPTION Dissolution rate and Permeability are the determinants  Critical Question? Soluble, unionized, moderately non-polar compounds only absorb How do polar drugs and nutrients such as glucose, amino acids absorb and distribute to target tissues?  Absorption  Distribution  Elimination  Gastrointestinal Membrane Phospholipids are amphipathic- polar and non-polar groups Non-polar groups face inwards and polar groups outwards  Mechanism of Drug Absorption 1. Passive transcellular or intracellular transport 2. Passive paracellular or intercellular transport 3. Carrier mediated transport Facilitated e.g. Cephalosphorins, Vitamin 12 Active- e.g 5-fluorouracil or 4. Vesicular transport- particulates and macromolecules 5. Drug Efflux pumps- Eg. p- glycoprotein  Passive Drug Diffusion  Through cells or between cells  Passive diffusion is governed  -by Fick’s Law dM/dt = DSK (Cd-Cr) / h dM/dt = PSCd  Driving force  -Concentration gradient  Mostly lipid drugs – thru membranes (