COURSE ORIENTATION FACTORS :

Intrinsic
Biopharmaceutics Pharmacodynamics Formulation
more on formulation -

Response and physiologic

physicochemical properties toxicity Pathologic
-

Liberation absorption
,
ng
active ingredient from Bioavailability (F)
the dosage form fraction of unchanged active drug that reaches the systemic
hindi lahat ng drugs circulation following whatsoever Rout of Administration

liberation convertible to percent

ay may ;

Sa solid dosage form 0 9

.
means 90 % of the drug appear on the blood ;

lang meron not metabolize , and active pa

(F) onti lang
:
Requiremt need napupunta problem sa
:

and low sa argo may

gamot by madissolve Dosage form

·

LACTOSE (commons
Dissolution rate-limiting step slowest determining Rout of Administration
;

rate step
-

for buraki
:

uses

liberation of Intrinsic Activity natural Activity ↑ DILUEUT MERI

;

ng rate : =

-no problem
liberation * nasa API ,
gamot
Formulation maraming I am an ng

Pharmacokinetics *
preparation tablet DILUEUT
:

concentration ng gamot compressed tablet

sa body fluid ↑ BIDER hindi madisintegrate need LUBRICAUT

: :

and nindi madissolve the

change liberate
:
now cone, active
-

Two compartments Central systemic circulation Dependent binder STARCH DISI T GRANTS
: :

1 .
to common

Peripheral tissues Disintegrants STARCH

2 .

peripheral each other :

↓
↑ central :

Peripheral
↑ LUBRICANT :
can harden the

which is better ? tablets

central compartment para pumunta gamot a

target sites ;
Physiologic & Pathologic
malipon a peripheral compartment (mga fats ,
ayaw * Patient dependent
maipon)
Drug Disposition
:

LADME

Bioequivalents
:

Difference SubCU & IM

prolong duration of action compare Generic & Innovator Drug

* when the drug is toxic once may expire pede

;

* reduce dosing frequency Kopyanin no iba

/
compliance
When Inhalational :

Rationalize volatile
;

not Oxygen propellant

:
;

Dose when innaler :

Dosage form spray ; ventolin

Clinical efficacy aerosol

LUNA >
A IPE

Absorbable / Reabsorption Excritable

non-polar Polar

Unionized Ionized

Lipophilic Hydrophilic

generally speaking drugs

Biotrans
are LUNA 3
HIPE

most drugs AnTIBIOTIC

creatinine clearance serv creatinine

KIDNEY PROBLEM
normal ↓ > ↑ creatinine
related
inversely blood
metabolic sa

of Muscles
no
problem Sa ICC 1 Serume
MODULE 1:
Introduction to Biopharmaceutics
and Pharmacokinetics
 What is a Drug?
substance that modify
any
E

regulatory molecules

T Endogenous ligands
Kanit and Kumabit sa RECEPTORS
neurotransmitter
normones
I .
Na Chanel Blockers pituitary .

hypothalamus
I CHOUS ,
most
biologically active of biomolecules

1 B-blockers receptors

voltage gated on channel-antiarrhythmics

Carrier CHous/ Active
I .
K Channel Blocker transporter

Enzyme
Structural CHOn (Tubulin)
IV . Calcium Channel Blocker not
regulatory protein
Class 1A Na Channel Blocker SO +AlOI
IA
Amiodarone Receptors
. :

Quinidine 1 Ligand gated on channel

(lonotropic)
[
.

fast
Procainamide 2 . GPCR's / Metatotropic Receptors
Disoprommide 3
Enzyme-linked Intermediate
=
.

verapis 4 Gene Transcription Receptor longest Kinetics

:

Class #B Diltiazem
IP .

Mexistine

Tocainide

Lidocaine First papasok potassium

second Calabas sodium
Phenytoin
↳exchanger
Third papasok calcium
Class 1C .

IC

Moricizine

lorcainide Inhibitor

Digoxin Interaction DYNAMICS

:

Flecainide

Encainide +OxiC
Propafenone
Potassium less electrolyte
:
↑ Digoxin

Dynamics
nawala and K :pangontra sa Digoxin
so action ni Digoxin
Biopharmaceutics
Study of the relationship between nature and intensity
of biologic effects and the various formulation factors

Nature and intensity of biologic effects ≈ total amount of

drug available to the body

Rate of drug delivery ≈ effectiveness of dosage form

Science that examines the interrelationship and effects

of the:
Physicochemical properties of the drug
Dosage form
Route of administration

↑
 is
priority safety
(safety)
Pre Clinical Animal Dose (LD50)
=

Lethal

Pharmacokinetic testing (Clinical Trial (

I normal na tao
I .
healthy volunteers
(safety (
Pharmacokinetic property :
Dose/Dosage Form

I with the target

pis disease Efficacy
=

# various wt variants of the target disease COMPARATOR

IV .
Post marketing Surveillance (PMS) standard drug/reference
drug
L
investigate parin RELIABLE
Efficacy more
-bakd May S/E :

*
I best than DOU
I no control observe under
;

* I
than DOC
real World condition
 #24
total bio-A is yung
amount that go to the
cunmetabolized
na gamot
blood :

ACTIVE PA
amount of unchanged
↑

Bioavailability Liquid dosage form :

fast Bioavailability

solid
slow to achieve target
concentration in blood

The extent of drug absorbed from a dosage form

The relative amount of drug from an administered

dosage form which enters the systemic circulation and
the rate at which it appears in the blood stream.

Varies due to differences in formulation, physiologic and

pathologic states of patients common factors :

Dosage form
2 .
Physiological State or

Pathological State
 # 24
left stomach

left side nakahiga :

delay bioavailabily
right side mabibilis maabsorb intestinal canal
:

mas
;

mas bababa ng

Malabsorption syndrome
:

patients with abnormalities of intestinal structure

major sites of absorption : small intestine

kulang ng carrier ,
proteins , absorbing nutrients
-

common Route of Administration na ibariba and formulation Kaya

iba .
in a in and Bioavailability
Intravenous %; rapid Wald ABSORPTION
:

100
;

most no

process of transport
of the drug to the

blood

large valum e es
Im
<100 :
subcutaneous

Oral first
]5 of pass effect
cause
to 200 %
2
Inhalational stomach
palang
most convenient
>
rapid onset may nasira na
agad
-

non invasive
Rectal 38-2100 %; mas mata as ng gamot mo

bioavailability ORAL : ↑ FPE nuwag na

:

sa

Disadvantages
:

Stigma (nakakahiya) inumin

Transdermal Super taas Bio-A but slow absorption

major organ for distributing DRUG blood

:

major site for metabolism :

liver

major site for elimination Kidney

:
Biopharmaceutical Studies
Aims to:

• Develop a dosage form that will provide consistent

bioavailability

• Establish mathematical models to describe the

absorption and disposition of the drug in the body.
Disposed active sa system
mo ADME (Pharmacokinetics)
:
 Protein binding displacement # 9
- not common Penicillin)
(naproxen ,

Pharmacokinetics Clinical
Pharmacokinetics

Pharmacodynamics
What body
the
drug does to the

Molecular Action/Biomolecule effect

I
proteins

Pharmacotherapeutics
Clinical application of drug
focused on all matters
Pharmacokinetics
#9 #9
central compartment
focuses on the study of SDC's (serumbrug concentration)
;

and I infusion
other fluid including factors that concentration danandahan patak
-

affect these ang

↳
peripheral compartment

-
to achieve maximum conc.
Pharmacodynamics curves

Maximum Achievable Response

~ "sigmoidal
"Ceiling
SDC
Dose

Response ------
i
ED50/ Potency dahan dan an

Time

Log Dose

Intermittent In Bolus nawawala gamot balik

:

Wala
:

Reason bakit ginagamit 'masyado Mabilis and elimination rate

L
constant ng gamot
Pharmacokinetic Curve
M repeat dosign

W
marami
and gamot
IV Bolus
-
-

one time

SDC

mabibilis mawawal a
inom
end
·
-
maximum effective conc .
/

maintain
minimum toxic concentration
maintain a Therapeutic
*

Time a
Range
Monica

inami
trange
↑ ...
first inom gamot
First Order
↓DC
*

-concentration dependent minimum Sub therapeutic

effective level
-most drugs will obey this concentration

Time
protein binding displacement #9
not common

Drug Interaction na nagpapatas ng drug cons .

⑧ protein binding Displacement

Albumin
-
W
~

Kabit

Drugs highly protein bound

-
:

naproxen
Propano 10
warfarin
Penicillin

Cloxacillin

Inhibition
gamot may Kasabay no bang gamot IHIBIT METABOLISM
=

TOXICITY

Induction
ACTIVATE HG METABOLISM
THERAPEUTIC FAILURE

clinical pharmacokinetics :

:
safe and gamot
2 .

effective and gamot

 cardio selective -
Betax 8101

Intensity of Drug Dose (B-1 Selectives

unpredictable toxicity
Amount of the
targetsite
drug reaches
-

Lipid soluble
opthalmic there is systemic effect ~

Absorption (Dominant
:

intestines
-

small

Factor
:

Crohn's Disease

Pharmacokinetics & Pharmacodynamics Renally

-
urine
excreted

P
And and magdikta ng Intensity ng epekto nq gamot :

1 .

Dependent on
drug dose Renally excreted URIE
2 .
Amount of drug that reaches the target site Billiary excreted : FECES
2

may absorption except IV Absorption Dominant

:

small intestine

Oral Factor :
eronn's Disease

subirigual namamaga bituka

Buccal Bioavailability
-

lower

Inhale

Eyes systemic
-

not
purpose ; a mata lang talaga
Opthalmic -

may systemic effect local

effect

Glaucoma · 10P

aquaeous 1 Tim0101

2 .

Metipranolol Broncho constriction

3 .
Carteolol 1-3 ; 5

4 Betaxolol (B-1 selective)

;

safest
5 .

Levo Dunolo

Suppository lanat may first pass effect (except IV)

Sile of Distribution na hindi dapat puntahan Sana

:

ADIDOSE & PROTENS

drugs that Dirbil

are lipid unpredictable
*

soluble
toxicity
*
way highly
apid soluble
:
na
drug
OLDER/GERIARICS
 Bio availability

Applications of PK studies and F Measurements

• Initial design of a drug dosage regimen
• Determine the reasons for:
F problems sobra naabsorb

Unusual distribution and elimination problem a carrier (rectal

kinetics Pharmacogenetic and

role and genes

pharmacogenomic effects
may
patient (metabolism)
nagkakaiba and a genes
genetic polymorph

Unusual drug response

Extent of patient compliance
Medication errors
Drug interactions
TDM
Regimen :

Dosage form Therapeutic Drug Monitoring (TDM)

Route of Administration

Dosing Frequency

Reasons for
:

& Medication
:

Bioavailability problems Interaction

errors or
Drug
⑫ Genetic variations involve
Unusual protein
;

:
; Genetic carrier

transporter
⑳
I
Whole
Pharmacogenomics genome nagkakaroon
:

ng
pagkakaiba sa
genetic Arg affinity/single
:

METABOLISM

-may kulang/sobre
genetic polymorphism
9
↳Oxidation Cyp

2DG - sinisiva antidepressant

anti psychotics
209
DHASE
2019
I
b .
Alcohol Dehydrogenase
C .
Pseudocholinesterase

D Acetylation
d .
↑
NAT ↓NAT
1 .

Asians Caucasians
2
:

2 .
Egyptians
fast acetylators 3 Western
.

Europeans
4. Mediterre
nean Jews

& Glucoronic
UDD - G +

28 GSA Conjugation
The Human Body
- An organism
 P -GP bomba palabas
mechanism Plasmodium falciparum (malarial
:

Transport
-

↓
1 .
Passive Diffusion
Chloroquine resistant
majority of the drugs
-

-concentration dependent kinetics

-along conc .
gradient Intestinal P-GP-tagabomba ng gamot

~nigh to low ; downhill -decrease absorption of orally drug

-

no carrier , no ATP ; no active transporter

P-GP substrate bomba ! BIOAVAILABILIM
-palabas
2 .
Active Transport DIGOXI -

low dose 25Mcg

=

TO XIC

-low to high
energy ; carrier
;

active transporter P-GD Inhibitor Sinabay sa P-GP substrate

;

bawal isabay sa

capacity limited/Satu substrate

cause toxicity
-

rated/
.
3 Facilitated Diffusion non
linew/ 1 .

verapamil
concentration ; downhill zero order/Michaelis nifedipine
-

along 2 .

Kinetics menten
-

no
energy 3 .
Chlorphenamine
-
carrier carrier mediated 4 .

Desipramine
Drugs : 5
Cyclosporine
phenytoin G Azithromyein

[
.

salicylates 7 Carvedicol
.
(Diabetes & Hin)
TOXIC
4 .

Pinocytosis Fluoxetine (SSRIs) 8 .

Amiodarone (Anti-arrythmial
pores may H20 displatin 9 . Nirmatrevir -

Lopinavir
cell drinking omeprazole 10 .
Flipansevin (Female viagra)

Alcohol II . Quinidine

5
Endocytosis 12 Procainami de
.

-pumapasok a cell 13 . Ranolazine

Engulement POSACOn920 le
-

14 .

cell eating Isavuconazole

-

15 .
-> Savuconazole

12 .
Itracona 20 le

a Exocytosis
NT release
P GP Inducers bomba
nagpapadami na
-
-

Therapeutic Failure

:
Rifampin
2 .
CB2 CYP3A4 dominant
3 .

Phenytoin oxidizer
4 St.
.
Junn's Wort

5 :
Green ted
 DifferentStructure
same effect

Theories of Drug Activity

Structurally Non-specific Drugs
• Pharmacologic action is not directly dependent on the
chemical structure of the drug but more on the
physicochemical properties of the compound

• Chemical structures may vary but the pharmacologic

actions are similar

• Slight modification in chemical structure has no

dramatic change in pharmacologic action
Theories of Drug Activity
Structurally Specific Drugs
• Pharmacologic action is directly dependent on the
chemical structure of the drug

• Slight modifications in chemical structure may produce

dramatic change in pharmacologic action
Drug-Receptor Interactions
What are receptors? macromolecules

• Large protein molecules embedded in

the cell wall or membrane
• Specific molecules that bind drugs
chemically forming a complex that
exerts a pharmacological action
• Traditional model: “Lock and Key”
↓ ↓

receptor drug

Emil Fischer ,
1894
Other Drug-Receptor Theories

Hypothesis of Clark

“The pharmacologic effect of the

drug depends on the percentage of
the receptors occupied”
Other Drug-Receptor Theories
Hypothesis of Ariens and Stephenson

“The effectiveness of a drug lasts as long

as the receptor is occupied”

• It is also called the Occupation Theory

• Affinity and intrinsic activity

Lighten natural activity
Other Drug-Receptor Theories
Hypothesis of Paton
“The effectiveness of a drug does not
depend upon the actual occupation of the
receptor by the drug, but upon obtaining
the proper stimulus”
OBSOLETE
THEORY t :

Agonist mabilis Kakabit mabilis

matagal
matanggal receptor

.. antagonist mabilis

• It is also called the Rate Theory

• Dissociation and association of agonist
and antagonist drugs
Other Drug-Receptor Theories
Induced-Fit Theory

• The receptor is partially flexible

• The shape of the active site on the
receptor changes when the drug binds
to the receptor
 LOCK & KAY

Other Drug-Receptor Theories IDUCE FIT

Macromolecular Perturbation Theory

protein

• The theory explains the interaction of a

drug and a receptor resulting to specific
and non-specific conformational
perturbation
Other Drug-Receptor Theories
Two State Receptor theory

• When a drug binds to a receptor, this

promotes a change in receptor state
from inactive to active state

• Once in the active state, it will elicit a

biological response.
Drug-Receptor Interaction
Important factors to consider:
• Affinity
• Efficacy / Intrinsic Activity
• Specificity