OUR LADY OF FATIMA UNIVERSITY

College of Pharmacy

BIOPHARMACEUTICS &
PHARMACOKINETICS
PHBP 311

Bioavailability and Bioequivalence Studies

WEEK 17
UNIT OUTCOMES

At the end of this module, the students are expected to:

Describe the drugs that require bioavailability and

bioequivalence studies
Enumerate the requirements necessary for the conduct of
bioavailability and bioequivalence studies
Interpret raw data of bioavailability and bioequivalence
studies
CHECKLIST

 Read course outcomes

 Read course guide prior to class attendance

 Proactively participate in discussions

 Watch videos related to the topic

 Participate in discussion board (Canvas)

 Answer and submit course unit tasks

REQUIRED READINGS/VIDEOS

Please watch the following videos thru the

given link.
https://www.youtube.com/watch?v=rv2Rpdi7OHM
NOTE: This has been assigned to you by your
instructor during the previous meeting.
• BIOAVAILABILITY STUDIES
• used to define the e ect of changes in the
physicochemical properties of the drug substance
and the e ect of the drug product (dosage form) on
the pharmacokinetics of the drug
• BIOEQUIVALENCE STUDIES
• used to compare the bioavailability of the same drug
(same salt or ester) from various drug products
 RELATIVE ABSOLUTE
AVAILABITY AVAILABILITY
Availability of the Systemic availability of
drug from a drug a drug after
product as compared
EXTRAVASCULAR
to a recognized
ADMINISTRATION
standard
compared to IV dosing
RA = [AUC]A AA (F) = [AUC]po / dose po
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[AUC]B [AUC]IV / dose IV

SAMPLE PROBLEM (ABSOLUTE AND RELATIVE
AVAILABILITY)

The bioavailability of a new investigational drug was

studied in 12 volunteers. Each volunteer received either
a single oral tablet containing 200 mg of the drug, 5
mL of a pure aqueous solution containing 200 mg of
the drug, or a single IV bolus injection containing 50
mg of the drug. Plasma samples were obtained
periodically up to 48 hours after the dose and assayed
for drug concentration.
 It is possible for the relative bioavailability to be greater than 100%
METHODS OF ASSESSING BIOAVAILABILTY

 PLASMA DRUG CONCENTRATION

 TMAX, CMAX, AUC

 URINARY DRUG EXCRETION

 Du, dDu/dt, t

 ACUTE PHARMACODYNAMIC EFFECT

 EMAX

 CLINICAL OBSERVATIONS
 WELL CONTROLLED CLINICAL TRIALS

 IN-VITRO STUDIES
 DRUG DISSOLUTION
PLASMA DRUG CONCENTRATION

• most direct and objective way to determine systemic drug

bioavailability
1. tmax = time required to reach plasma drug concentration
rate of absorption = rate of elimination
2. cmax = maximum plasma concentration
provides that the drug is su ciently systematically absorbed to provide
therapeutic e ect

3. AUC = measurement of the extent of bioavailability

total amount of rug that reaches the systemic circulation
proportional to dose
 URINARY DRUG EXCRETION
• Indirect method
• Unchanged in the urine
• Timely urine sample must be collected

Du = cumulative amount of drug excreted in the urine

dDu/dt = rate of drug excretion
depen. k and Cp

t = time for the drug to be excreted

useful parameter in BE studies
ACUTE PHARMACODYNAMIC EFFECT

For locally acting, non systematically absorbed

drug product plasma drug concentrations may not reflect
the bioavailability of the drug at the site of action.
not intended to deliver the active moiety to the
bloodstream for systemic distribution
PARAMETERS:
total Area under the APE – time curve
peak pharmacodynamic e ect
time for peak pharmacodynamic e ect
CLINICAL OBSERVATIONS
• LEAST accurate, LEAST sensitive, LEAST reproducible
the general approaches for determining in vivo BA
IN-VITRO STUDIES
• The test formulation that demonstrates the MOST
RAPID RATE OF DRUG DISSOLUTION in vitro will
generally have the MOST RAPID RATE OF DRUG
BIOAVAILABILITY in vivo
BIOPHARMACEUTICS CLASSIFICATION SYSTEM
(BCS)
Calculating what volume
Based on aqueous solubility of drug
of an aqueous medium and the
is su cient to dissolve
permeation of the drug through GI tract
highest anticipated dose

CLASS SOLUBILITY PERMEABILITY

SOLUBILITY 1 HIGH HIGH

PERMEABILITY
DISSSOLUTION 2 LOW HIGH

3 HIGH LOW

4 LOW LOW
MULTI DRUG PRODUCT

Is a drug product that contains the same active

drug substance in the same dosage form and is
marketed by more than one pharmaceutical
manufacturer
SINGLE SOURCE DRUG PRODUCTS

Patent has not be expired or has certain

exclusivities so that only one manufacturer
can make it
APPROVED PRODUCTS WITH THERAPEUTIC
EQUIVALENCE EVALUATIONS ( ORANGE BOOK)

Identifies drug products approved on the

basis of by the FDAsafety and e ectiveness
PHARMACEUTICAL PHARMACEUTICAL
EQUIVALENT ALTERNATIVE

SAME Same THERAPEUTIC

MOIETY
Active ingredients
Salt BUT… as di erent
Dosage form and Salt
strength
Dosage form and
ROA
strength
Content uniformity
Which of the following drug products are
considered to be pharmaceutical alternatives?
A. cephalexin 500 mg cap & cefalexin 500 mg
cap
B. propranolol 10 mg tab (branded) &
propranolol 10 mg tab (unbranded)
C. nifedipine 5 mg cap & nifedipine 20 mg mg
GITS tab
D. ranitidine HCl (local) 150 mg tab &
ranitidine HCl (imported) 150 mg tab
Which of the following products are considered to be
pharmaceutical equivalents?

A. Mefenamic acid 250 mg cap & mefenamic acid 500

mg cap
B. amlodipine besylate (innovator) 10 mg tab &
amlodipine besylate (generic) 10 mg tab
C. amoxicillin 500 mg cap & amoxicillin 250 mg/mL
susp.
D. Clindamycin HCl 300 mg cap & clindamycin
phosphate 150 mg/mL amp x 4 mL
E. Paracetamol (Brand A) 500 mg tab & paracetamol
(Brand B) 500 mg cap
 THERAPEUTIC THERAPEUTIC
EQUIVALENT ALTERNATIVE

CONTAINS…
If they are….
SAFE AND EFFECTIVE DIFFERENT active
ingredients indicated for
PHARMACEUTICAL
the SAME therapeutic
EQUIVALENT
use
BIOEQUIVALENT
ADEQUATELY LABELED
COMPLIED WITH CGMP