Introduction to Biopharmaceutics (and Pharmacokinetics)
IP 155 Laboratory Daryl E. Kayanan
Biopharmaceutics
Drug in dosage form
Pharmacodynamics
Pharmacologic effect
Liberation
Drug in contact with bodys membranes
Degradation
Drug particles in body fluids/cavities
Site of action
Dissolution
Drug in solution
Peripheral Tissues
Distribution
Absorption
Blood/Plasma Liver
Free Bound
Metabolism
Pharmacokinetics
Excretion
Elimination
Kidneys
Biopharmaceutics
Biopharmaceutics is the study of the interrelationships between the physical and chemical properties of the drug, the design and choice of its system of drug delivery, and the expected therapeutic response after its administration to the patient Biopharmaceutics is interrelated with Physical pharmacy Medicinal chemistry Pharmacokinetics Formulation
Biopharmaceutics
Pharmaceutics + Bio interdependence of biological aspects of the living system and the physical-chemical properties that govern the preparation and behavior of the drug Liberation + Absorption
Dissolution
Solubility
Salt forms
Diffusion Bioavailability
Absorption Dosage forms
Gastric emptying
Permeability
Bioequivalence
Route of administration
Pharmacokinetics
Kinetics of drug absorption, distribution, and elimination Deals with the time course of drug in the body (ADME)
Drug at site of absorption Drug is absorbed Drug is distributed to different tissues
Disposition
Drug is metabolized
Elimination
Drug is excreted by the body by different means
Drug concentration-time profile
Characterization of the time course of a drug inside the body
Administration of the same dose of different drugs to the same individual will produce different conc-time profiles. This is because different drugs have different absorption and disposition characteristics Administration of the same dose of a drug to different individuals will produce different conc-time profiles as well the same drug can be absorbed, distributed, and eliminated at different rates in different individuals
Pharmacokinetics
Each process or processes combined is associated with one or more pharmacokinetic parameters describe or determine the rate and/or magnitude of the different processes
Examples Half-life (t1/2)
how long would a drug stay in the body
Absorption rate constant (ka)
Factor that determines how fast can a drug be absorbed at a specific site of action
Clearance
Capability of a drug to be cleared from the bloodstream or by an organ, which may either proceed to elimination or distribution to other tissues
Rates and Orders of the Pharmacokinetic Process
The rate
Instantaneous speed at which a process occurs (ex. Rate of drug absorption = amt absorbed per unit time)
The Rate Constant
Factor that determines the rate of the process
The Order
Determines how the amount of the drug involved will influence the rate of the process
Orders of pharmacokinetic processes
Zero-order process Constant rate constant amount of drug involved in the process C = Co - kt First order process Constant percentage of drug involved rate is proportional to the amount of drug involved in the process ln C = ln Co - kt
Drug Absorption
Definition: Absorption is the rate and extent at which drugs reach the systemic circulation from the site of drug administration
Thus A drug has been absorbed if it has reached the systemic circulation Also Drugs directly administered into the bloodstream are assumed to be 100% absorbed
Drug Absorption
Drugs administered extravascularly would not have 100% absorption. Biopharmaceutics is concerned with the factors affecting drug absorption, as well as factors affecting drug liberation 2 fundamental parameters that govern drug absorption:
Solubility Permeability
Bioavailability (F)
The fraction of drug dose of unchanged drug that reaches the systemic circulation
The rate and extent to which the API is absorbed from the drug product and becomes available at the site of action
F = Fa x Fg x Fh
Fa = fraction of drug absorbed Fg = fraction of drug that escapes gastrointestinal metabolism Fh = fraction that escapes first-pass effect
Bioequivalence
Two drug products (same API) are bioequivalent if after drug administration of the same molar dose, their bioavailabilities are the same and provide similar effects with respect to safety and efficacy. Should apply both in single or multiple administrations Results in vivo reflect the biopharmaceutics of the drug product The goals of generic drugs are to be bioequivalent with the innovator drug
Pharmacokinetic basis of bioequivalence
Based on these 3 parameters: 1. Maximum drug concentration (Cpmax) 2. Time to peak (tmax) 3. AUC (AUC0t(last) and AUC0)
