PHBP 211: Biopharmaceutics and Pharmacokinetics

LECTURE 1: INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS

JEWEL D.C. BARLIS – FACULTY OF PHARMACY
FIRST SEMESTER | A.Y. 2023 – 2024

INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS DRUG THERAPEUTIC RANGE

mg/L
LECTURE OUTLINE
Digoxin 0.5 – 2.1
Amiodarone 1.0 – 2.5
Salicylate 150 – 300
BIOPHARMACEUTICS
Theophylline 10 – 20
Phenytoin 10 - 20
• The science that examines the interrelationship of the
physicochemical properties of the drug, the dosage form Carbamazepine 5.0 - 12
in which the drug is given, and the route of administration
on the rate and extent of systemic drug absorption.
EXPERIMENTAL PHARMACOKINETICS
• The study of the chemical and physical properties of
drugs, their components, and their activities in living • development of biologic sampling techniques, analytical
methods for the measurement of drugs and metabolites
organisms.
and procedure that facilitates data collection and
manipulation
BIOAVAILABILITY
THEORETICAL PHARMACOKINETICS
• measurement of the rate and extent of systemic
absorption of therapeutically active drug • development of pharmacokinetics models that predict
drug disposition after administration
PHARMACOKINETICS ➔ IN VIVO- involves human subjects / laboratory animals

• The study of the time course of drug movement in the ➔ IN VITRO – employs test apparatus and equipment
body during absorption, distribution, and elimination. without involving human subjects / laboratory animals

L – Liberation
A – Absorption PHARMACOKINETICS
D – Distribution
• MODEL - a hypothesis using mathematical terms to
M – Metabolism
describe quantitative relationship concisely
E – Excretion
➔ Empirical
R – Response
➔ Physiological
➔ Compartmentally based
CLINICAL PHARMACOKINETICS
• PHARMACOKINETIC MODELS
• application of pharmacokinetic methods to drug therapy
➔ Catenary
• the study of the relationships between drug dosage ➔ Mammillary
regimens and concentration–time profiles ➔ Physiologic Pharmacokinetic

THREE FUNDAMENTAL PARAMETERS

PHARMACODYNAMICS
1. CLEARANCE - volume of fluid completely cleared of drug
per unit time • The study of the relation of the drug concentration or
amount at the site of action and its pharmacologic
2. VOLUME OF DISTRIBUTION - apparent volume into which response.
the drug has distributed to produce the measured
concentration CLINICAL TOXICOLOGY

3. ELIMINATION HALF-LIFE - time taken for 50% of the drug • The study of the adverse effects of drugs and toxic
to be eliminate substances in the body

POPULATION PHARMACOKINETICS
MEASUREMENT OF DRUG CONCENTRATIONS
• study of pharmacokinetics differences of drugs in
• Sampling of biologic specimen
various population
• Invasive Method
• TDM (Therapeutic Drug Monitoring) o requires surgical / parenteral intervention
o employed for very potent drug to optimize efficacy o sampling of blood, spinal fluid, synovial fluid,
and to prevent any adverse toxicity tissue biopsy

• CPKS (Clinical Pharmacokinetic Service) • Non- invasive method

o provides pharmacokinetic and drug analysis o without surgical/ parenteral intervention
services for safe drug monitoring o feces, urine, saliva

JHON MANUEL M. MATIAS 1

 INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS

BLOOD BIOPHARMACEUTICS

➔ highly specialized tissue composed of many different INVOLVES FACTORS THAT INFLUENCE:
kinds of components
a. Design of drug product
o Whole blood → clot → centrifuge → supernatant → SERUM
b. Stability of drug within the drug product
o Whole blood → (+) heparin → centrifuge → supernatant → c. Release of the drug from the drug product
PLASMA
d. Rate of dissolution/ release of the drug from at the
absorption site
IMPORTANCE OF MEASURING PLASMA DRUG CONCENTRATION e. Delivery of drug to the site of action

1. Adjustment of the drug dosage in order to individualize and

optimize therapeutic drug regimen. BIOPHARMACEUTIC CONSIDERATIONS IN DRUG
PRODUCT DESIGN
2. Provides guide to the progress of disease state.
`Therapeutic objective
3. Enable to modify the drug dosage accordingly.
➔ Drug (API)
➔ Route of administration
➔ Drug dosage and dosage regimen
➔ Type of drug product
➔ Excipients
➔ Method of manufacture

DRUG DISPOSITION

• the description of drug distribution and elimination

DRUG EXPOSURE
• MEC (Minimum effective concentration)
• the dose and various measure of acute or integrated
➔ needed to produce the desired pharmacologic effect drug concentrations in plasma and other biological fluid
• MTC (Minimum Toxic concentration)
➔ needed to just barely produce toxic effects DRUG RESPONSE

• ONSET OF TIME • the direct measure of the pharmacologic effect of the

➔ time required to reach MEC drug

• PEAK TIME
➔ time of Maximum drug conc in the plasma and a rough DESIGN OF THE APPROPRIATE DOSAGE FORM OR
marker of average rate of drug absorption DELIVERY SYSTEM DEPENDS ON:

1. Physical and chemical properties of the drug

• PEAK CONCENTRATION
➔ maximum drug concentration 2. Dose of the drug
3. Route of administration
• DURATION OF DRUG ACTION
➔ difference between the onset of time and time for the 4. Type of Drug system desired
drug to decline back to MEC 5. Desired therapeutic effect
6. Physiologic release of the drug from the delivery system
• AUC (Area Under the Curve)
➔ amount of drug absorbed systematically 7. Bioavailability of the drug at the absorption site

➔ total area found under the plasma concentration vs 8. Pharmacokinetics and pharmacodynamics of the drug
time curve from the initial dose to final elimination of the
drug from the body PHYSICOCHEMICAL PROPERTIES

A. Drug Dissolution
RELATIONSHIP BETWEEN THE DRUG, THE DRUG
B. Drug Solubility
PRODUCT, AND THE PHARMACOLOGIC EFFECT
C. Particle Size and Surface Area
Drug release Drug in systemic Drug in D. Partition Coefficient and Extent of Ionization
and dissolution circulation tissues
E. Salt Formation
F. Polymorphism
G. Chirality
Excretion and Pharmacologic H. Hydrates
metabolism or clinical effect I. Complex Formation

JHON MANUEL M. MATIAS 2

 INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS

DRUG DISSOLUTION POLYMORPHISM

• the rate at which the solid drug enters into solution is • the ability of a drug to exist in more than one crystalline form
often the rate limiting step in bioavailability.
• Amorphous, or noncrystalline forms of a drug have
THE NOYES-WHITNEY EQUATION describes the diffusion- faster dissolution rates than do crystalline forms.
controlled rate of drug dissolution
Same CHEMICAL Different PHYSICAL
STRUCTURE PROPERTIES
DRUG SOLUBILITY

• in a saturated solution is a static (equilibrium) property CHIRALITY

• The dissolution rate of a drug is a dynamic property
related to the rate of absorption • the ability of a drug to exist as optically active
stereoisomers or enantiomers
PARTICLE SIZE AND SURFACE AREA
• INDIVIDUAL ENANTIOMERS may not have the same
• inversely related pharmacokinetic and pharmacodynamic activity.

• As solid drug particle size decreases, particle surface FOR EXAMPLE, ibuprofen exists as the R- and S- enantiomers;
area increases. only the S-enantiomer is pharmacologically active.

↓PS → ↑ SA

PARTITION COEFFICIENT

• the ratio of the solubility of the drug, at equilibrium, in a

non-aqueous solvent

• inc in the number of carbons

• decrease water solubility

EXTENT OF IONIZATION

• Drugs that are weak electrolytes (acids or bases) exist in

both an ionized form and a nonionized form in solution.

• The extent of ionization depends on the pKa of the weak HYDRATES

electrolyte and the pH of the solution.
• Drugs may exist in a hydrated, or solvated form or as an
• the ionized form is POLAR, and therefore more WATER anhydrous molecule
SOLUBLE, than the nonionized form
• DISSOLUTION RATES differ for hydrated and anhydrous
forms.
PARTITION COEFFICIENT AND EXTENT OF IONIZATION

THE HENDERSON-HASSELBALCH EQUATION - describes COMPLEX FORMATION

the relation between the ionized and the nonionized forms of
a drug as a function of pH and pKa • A COMPLEX is a species formed by the reversible or
irreversible association of two or more interacting molecules
pH = pKa 50% ionized or ions.
50% unionized
• CHELATES are complexes that typically involve a ring-like
structure formed by the interaction between a partial ring of
SALT FORMATION
atoms and a metal
• the choice of salt form for a drug depends on the desired EX. hemoglobin, insulin, cyanocobalamin
physical, chemical, or pharmacologic proper ties
• Complex formation usually alters the physical and
provide slower dissolution greater stability
chemical characteristics of the drug.
slower bioavailability less local irritation at the
absorption site • Large drug complexes, such as drug-protein complexes, do
longer duration of action less systemic toxicity not cross cell membranes easily.

WEAKLY ACIDIC DRUGS WEAKLY BASIC DRUGS • FOR EXAMPLE: The chelate of tetracycline with calcium is
less water soluble and is poorly absorbed.
Potassium Hydrochloride
Sodium Salts Sulfate
Citrate
Gluconate Salts
Estolate
Napsylate
Stearate Salts

JHON MANUEL M. MATIAS 3

 INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS

LADMER SYSTEM

LIBERATION

• delivery of the active ingredient from a dosage form into

solution

• THE FIRST STEP which determines onset of action, rate

of absorption, availability, etc., which is true for all drug
products by all routes of administration (except
intravenous and the peroral use of true solutions)
controlled by the characteristics of the drug product.

➔ Disintegration
➔ Dissolution

DISINTEGRATION

o state in which any residue of the tablet, except fragments of

insoluble coating, remaining on the screen of the test
apparatus in the soft mass have no palpable firm core

DISSOLUTION

o the process by which a chemical or drug becomes

dissolved in a solvent

RATE LIMITING STEP

• the process with the slowest rate constant in a system of

simultaneous kinetic processes

JHON MANUEL M. MATIAS 4