UNIT 1: INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS

TERM DESCRIPTION
MEC Minimum Effective
OUTLINE Concentration
I BIOPHARMACEUTICS If the drug concentration at the
A Biopharmaceutics Factors
site of action exceeds the MEC,
II PHARMACOKINETICS
A Experimental approach a pharmacologic response
B Theoretical Approach result
C Statistical method BIOAVAILABILITY a measure of systemic
D Classical Pharmacokinetics availability of a drug may differ
III CLINICAL PHARMACOKINETICS from one drug product to
A. Population Pharmacokinetics another containing the same
B. TDM drug, even for the same route of
C. CPKS
IV PHARMACODYNAMIC
administration.
A. Pharmacodynamics and Pharmacokinetics Models CRITICAL The most important steps in the
V TOXICOKINETICS AND CLINICAL TOXICOLOGY MANUFACTURING manufacturing process
A. Toxicokinetic VARIABLES
B. Toxicokinetic Data
C. Toxicokinetic Studies PHARMACOKINETICS
D. Clinical Toxicology
VI MEASUREMENT OF DRUG CONCENTRATIONS  is the science of the kinetics of drug absorption,
A. Sampling of Biologics Specimens distribution, and elimination (ie, metabolism and
B. Drug Concentration in Blood, Plasma or Serum excretion). The description of drug distribution and
C. Plasma Drug Concentration- Time Curve elimination is often termed drug disposition.
D. Drug Concentrations in Tissue Characterization of drug disposition is an important
E. Drug Concentration in Urine and Feces prerequisite for determination or modification of dosing
F. Drug Concentration in Saliva regimens for individuals and groups of patients.
G. Forensic Drug Measurement
H. Significance of Measuring Plasma Drug Concentration
 study of pharmacokinetics involves both experimental and
theoretical approaches.

BIOPHARMACEUTICS SUBTOPIC
 It is the science that examines the interrelationship
physiochemical properties of the drug, the dosage form EXPERIMENTAL APPROACH
(drug products) in which the drug is given, and the route of Involves the development of biologic sampling techniques,
administration on the rate and extent of systemic drug analytical methods for the measurement of drugs and
absorption. metabolites, and procedures that facilitate data collection and
 The physiochemical characteristics of the active manipulation.
pharmaceutical ingredients, the dosage form of the drug, THEORETICAL APPROACH
and the route of administration are critical determinants of Involves the development of pharmacokinetic models that
the In vivo performance, safety and efficacy of the product. predict drug disposition after drug administration.
 Importance of the drug substances and drug formulation STATISTICAL METHOD
on the absorption and distribution of the drug.
o Drugs in its dosage form
Application of statistics is an integral part of pharmacokinetic
o Drugs reaction after being released from the studies. Statistical methods are used for pharmacokinetic
dosage form. parameter estimation and data interpretation ultimately for the
o Fraction of the drug absorbed from the site of purpose of designing and predicting optimal dosing regimens
administration to the circulatory. for individuals or groups of patients. Statistical methods are
o Drugs reaches the site of action. applied to pharmacokinetic models to determine data error and
structural model deviations.
BIOPHARMACEUTICS FACTORS
CLINICAL PHARMACOKINETICS
BIOPHARMACEUTIC FACTORS  It is the application of pharmacokinetic methods of drug
therapy
Biopharmaceutics involves factors that influence (1) the design  involves a multidisciplinary approach to individually
of the drug product, (2) stability of the drug within the drug optimized dosing strategies based on the patient’s disease
product, (3) the manufacture of the drug product, (4) the state and patient-specific considerations.
release of the drug from the drug product, (5) the rate of
dissolution/release of the drug at the absorption site, and (6)
delivery of drug to the site of action, which may involve
targeting the drug to a localized area (eg, colon for Crohn
disease) for action or for systemic absorption of the drug.
SUBTOPIC

POPULATION PHARMACOKINETICS
TERMINOLOGY

ADMIN 1
The study of pharmacokinetic differences of drugs in various accurate, and precise analytical methods are available for
population groups the direct measurement of drugs in biologic matrices.
Such measurements are generally validated so that
THEORETIAL DRUG MONITORING (TDM) accurate information is generated for pharmacokinetic and
Clinical pharmacokinetics is also applied to therapeutic drug clinical monitoring. In general, chromatographic and mass
monitoring (TDM) for very potent drugs, such as those with a spectro-
narrow therapeutic range, in order to optimize efficacy and to metric methods are most frequently employed for drug
prevent any adverse toxicity. concentration measurement, because chromatography
separates the drug from other related materials that may
cause assay interference and mass spectrometry allows
CLINICAL PHARMACOKINETICS SERVICE
detection of molecules or molecule fragments based on
Pharmacokinetic and drug analysis services necessary for their mass-to-charge ratio.
safe drug monitoring are generally provided by CPKS.
SUBTOPIC
PHARMACODYNAMICS
 refers to the relationship between the drug concentration SAMPLING OF BIOLOGICS SPECIMENS
at the site of action (receptor) and pharmacologic
response, including biochemical and physiologic effects Only a few biologic specimens may be obtained safely from the
that influence the interaction of drug with the receptor. The patient to gain information as to the drug concentration in the
interaction of a drug molecule with a receptor causes the body.
initiation of a sequence of molecular events resulting in a The measurement of drug and metabolite concentration in
pharmacologic or toxic response. each of these biologic materials yields important information,
such as the amount of drug retained in, or transported into, that
region of the tissue or fluid, the likely pharmacologic or
SUBTOPIC toxicologi outcome of drug dosing, and drug metabolite
formation or transport.
PHARMACODYNAMICS AND PHARMACOKINETICS
MODELS Invasive methods include sampling blood, spinal fluid,
Are constructed to relate plasma drug level to drug synovial fluid, tissue biopsy, or any biologic material that
concentration at the site of action and establish the intensity requires parenteral or surgical intervention in the patient.
and time course of the drug.
Noninvasive methods include sampling of urine, saliva,
TOXICOKINETICS AND CLINICAL TOXICOLOGY feces, expired air, or any biologic material that can be obtained
SUBTOPIC without parenteral or surgical intervention.

TOXICOKINETICS DRUG CONCENTRATIONS IN BLOOD, PLASMA OR

is the application of pharmacokinetic principles to the design, SERUM
conduct, and interpretation of drug safety evaluation studies Measurement of drug and metabolite concentrations (levels) in
(Leal et al,1993) and in validating dose-related exposure in the blood, serum, or plasma is the most direct approach to
animals. assessing the pharmacokinetics of the drug in the body.
Whole blood contains cellular elements including red blood
TOXICOKINETIC DATA cells, white blood cells, platelets, and various other proteins,
such as albumin and globulins. In general, serum or plasma is
Aid in the interpretation of toxicologic findings in animals and
most commonly used for drug measurement.
extrapolation of the resulting data to humans.

TOXICOKINETIC STUDIES PLASMA DRUG CONCENTRATION – TIME CURVE

It is generated by obtaining the drug concentration in plasma
Are performed in animals during preclinical drug development
samples taken at various time intervals after a drug product is
and may continue after the drug has been tested in clinical
administered.
trials.
As the drug reaches the general (systemic) circulation, plasma
drug concentrations will rise up to a maximum if the drug was
CLINICAL TOXICOLOGY given by an extravascular route.
is the study of adverse effects of drugs and toxic substances ABSORPTION OF A DRUG IS MORE RAPID THAN
(poisons) in the body. The pharmacokinetics of a drug in an ELIMINATION
overmedicated (intoxicated) patient may be very different from Elimination of a drug can proceedby excretion,
the pharmacokinetics of the same drug given in lower biotransformation, or a combination of both. Other elimination
therapeutic doses. At very high doses, the drug concentration mechanisms may also be involved, such as elimination in the
in the body may saturate enzymes involved in the absorption, feces, sweat, or exhaled air.
biotransformation, or active renal secretion mechanisms,
thereby changing the pharmacokinetics from linear to nonlinear MEC represents the minimum concentration of a drug needed
pharmacokinetics. at the receptors t produce the desired pharmacologic effects.
MEASUREMENT OF DRUG CONCENTRATION
 drug concentrations are an important ele-ment in MTC- represents the drug concentration needed to barely
determining individual or population pharmacokinetics, produce toxic effect.
drug concentrations are measured inbiologic samples,
such as milk, saliva, plasma, and urine. Sensitive,

ADMIN 2
ONSET TIME- corresponds to the time required for the drug to
reach the MEC REFERENCES

INTENSITY- It is proportional to the number of drug receptors

Notes from the discussion by
occupied.
DRUG DURATION OF ACTIONS- it is the difference between
the onset time and the time for drug to decline back to MEC. MCNP COLLEGE OF PHARMACY – MA. FILIPINA BARBA

PEAK PLASMA LEVEL- also known as MAXIMUM DRUG

CONCENTRATION ( MDC) is related to the dose, the rate
constant absorption and the elimination contact of the drug.

TIME FOR PEAK PLASMA LEVEL- it is the time of Maximum

Drug Concentration in the plasma and is rough marker of
average rate of drug absorption.

AREA UNDER CURVE- related to the amount of drug

absrobed systematically.

DRUG CONCENTRATION IN TISSUE

The measurement of the drug concentration in tissue biopsy
material may be used to ascertain if the drug reached the
tissues and reached the proper concentration with the tissue.

DRUG CONCENTRATIONS IN URINE AND FECES

Measurement of drug in urine is an indirect method to
ascertain the bioavailability of a drug. The rate and extent of
systemic drug absorption. Measurement of drug in feces may
reflect drug that has not been absorbed after an oral dose or
may reflect that has been expelled by biliary secretion after
systemic absorption.

DRUG CONCENTRATION IN SALIVA

The saliva/plasma drug concentration ratio is mostly influenced
by the pKa of the drug and the pH of the saliva. Weak acid
drugs and weak base drugs significantly different than 7.4
( plasma pH) which generally have better correlation to plasma
drug levels. The used salivary drug concentration as a
therapeutic indicator should be used with caution and
preferably as a secondary indicator.

FORENSIC DRUG MEASUREMENTS

Drug measurements in tissue obtained at autopsy or in a bodily
fluid such as saliva, feces, blood. The appearance of social
drugs in the blood, saliva, urine drug analysis shows short term
drug abuse. The analysis for drug abuse in hair samples is by
very sensitive assay methods, such as gas chromatography
coupled with mass spectrometry that provides information
regarding the past drug exposure.

SIGNIFICANCE OF MEASURING PLASMA DRUG

CONCENTRATIONS
The intensity of pharmacologic or toxic effect of a drug is often
related to the concentration of the drugs at the receptor site
that is usually located in the tissue cells. The monitoring the
concentration of drugs in the blood or plasma ascertains that
the calculated dose actually delivers the plasma level required
for therapeutic effect. It allows the adjustment of the drug
dosage in order to individualize and optimize therapeutic drug
regimens.

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