Biopharmaceutics and Pharmacokinetics Lecture Notes PDF

Biopharmaceutics and Pharmacokinetics Pharmacodynamics  Pharmacodynamics Drug actions and their mechanisms DRUGS RECEPTORS PHARMACOLOGICAL RESPONSES 2  Biopharmaceutics is the science that considers the interrelationship betw...

Biopharmaceutics and Pharmacokinetics Pharmacodynamics  Pharmacodynamics Drug actions and their mechanisms DRUGS RECEPTORS PHARMACOLOGICAL RESPONSES 2  Biopharmaceutics is the science that considers the interrelationship between the physicochemical properties of the drug, its dosage form and the route of administration on the rate and extent of drug absorption. Physicochemi- Physicochemi- Route of cal properties cal properties administration of drug of dosage form Rate (time frame) and extent (amount) of drug absorption  Pharmacokinetics is the study of the time course of drug journey in the body – absorption, distribution, metabolism, and excretion. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an – individual patient.  Fate of the drug Journey of the drug in the body is called Fate of the drug = what happens to the active ingredient (drug) in the body after administration of a drug product (dosage form) LADMER  Drug properties influencing its absorption - Solubility and PKa dissolution rate - Pka Drugs are: – Ions (strong - Permeability electrolytes) - Papp (Po/w) – Non electrolytes (steroids, sugars) – Partially dissociated  pH partition theory A weak acid ionizes ionize to form an anion (A-) and a proton (H+) Weak Base (B) ionize by accepting a proton (H+) to form a cation (BH+) All conc. are molar conc. [ H 3O  ]  [ A- ] Ka  [ HA] Take the log of both sides and multiply by -1 Henderson – Hasselbach equation [A- ] [I ] pH  log  pKa pH  log  pKa [ HA] [UI ] [ B] [UI ] pH  log  pKa pH  log  pKa  [I ] [ BH ]  I+N= 100 I  100 %ionization IN pH partition theory (cont.) For a weak acid 100 %ionization(acid )  1  anti log( pKa  pH ) For a weak base 100 %ionization(base)  1  anti log( pH  pKa) Absorption prediction Prediction for absorption Renal elimination of drugs enhanced by changing urinary pH to increase drug ionization and inhibits tubular re-absorption. Alkalinization of urine by NaHCO3 increases excretion of acidic drugs e.g. aspirin. Acidification of urine by vitamin C or NH4Cl increases excretion of weak base drugs e.g. amphetamine In drug poisoning,  The logP value is a constant LogP = log10 (Partition Coefficient) P = [organic]/[aqueous A positive value for A negative value for logP denotes a higher logP means the concentration in the compound has a lipid phase (i.e., the higher affinity for the compound is more aqueous phase (it is lipophilic). more hydrophilic); – LogP = 1 means there is a 10:1 partitioning in Organic : Aqueous logP = 0 equal partition between lipid and aqueous phases  Apparent partition coefficient Increasing polarity of the drug by: ionization,introduction of OH, COO-, NH2 , etc. increase in H2O solubility decrease in APC Decreasing the polarity of the drug by: introduction of methyl group, methylene group etc. decrease in H2O solubility increase in APC  Partition coefficient Uses: - In vitro guide to some cases of drug absorption From stomach, buccal cavity, colon and skin. - Not very accurate for absorption from intestine due to v.large surface area and multiple mechanisms of abs - Indicator of storage in fats.(barbiturates) Passive diffusion Fick’s First law of diffusion D: diffusion coefficient. Related to the size and lipid solubility of the drug and the viscosity of the diffusion medium. Lipid solubility or molecular size D thus dM/dt A: surface area. The surface the rate of diffusion x: membrane thickness. the quicker the diffusion. Concentration difference. The drug concentration in blood or plasma will be