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Biopharma
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Introduction to Biopharmaceutics (and Pharmacokinetics)
IP 155 Laboratory
Daryl E. Kayanan
Drug in dosage form
Liberation
Drug particles in
body fluids/cavities
Dissolution
Drug in solution
Degradation
Absorption
Liver
Metabolism
Blood/Plasma
Free
Distribution
Peripheral
Tissues
Pharmacologic effect
Pharmacodynamics Biopharmaceutics
Pharmacokinetics
Drug in contact
with body’s
membranes
Bound
Elimination
Kidneys Excretion
Site of action
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”
Solubility
Salt forms
Dissolution
Bioavailability
Gastric emptying Dosage forms
Diffusion
Absorption
Route of administration Bioequivalence
Permeability
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
Drug is metabolized
Drug is excreted by the body by different means
Elimination Disposition
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 (AUC0→t(last) and AUC0→∞)