PHBP Prelims - Reviewer
PHBP Prelims - Reviewer
PHBP Prelims - Reviewer
Pharmacokinetics
PHBP221 1
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 2
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 3
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 4
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 5
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Blood
Highly specialized tissue composed of many
different kinds of components
Good indicator for drug absorption and drug
elimination
Serum – no longer contain the clotting
proteins; does not contain fibrinogen.
Plasma – anticoagulant: heparin
Whole blood → clot → centrifuge →
supernatant → SERUM
Whole blood → (+) heparin → centrifuge
→ supernatant → PLASMA graph that shows the concentration of a drug
in the plasma after administration or over a
specific period of time
x-axis: independent variable, time
y-axis: dependent variable, plasma
concentration
MEC (Minimum effective concentration)
- Needed to produce the desired
pharmacologic effect
- Minimum concentration needed to
produce the desired therapeutic or
pharmacologic effect, wherein if the drug
is below MEC, it only produces a
subtherapeutic effect.
PHBP221 6
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 7
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Figure 1
Water: aqueous layer, polar
Octanol: non-aqueous layer, non-polar
Extent of Ionization
Need both polar enough and nonpolar
enough Drugs that are weak electrolytes (acids or
bases) exist in both an ionized form and a
C. Particle Size and Surface Area non-ionized form in solution.
The extent of ionization depends on the
inversely related
pKa of the weak electrolyte and the pH of
As solid drug particle size decreases, particle
the solution.
surface area increases.
- pKa: negative logarithm of the acidity
Low Particle Size = High Surface Area= High
dissociation constant, indicator or
Dissolution Rate (faster absorption)
measure of acidity of a substance
The powders have high dissolution rate than
The ionized form is POLAR , and therefore
the tablets
more Water soluble, than the non-ionized
The pharmaceutical solutions have high
form
dissolution rate than the powders
- Ionized form: polar, water soluble,
hydrophilic, lipophobic
- Non-ionized form: non-polar,
liposoluble, lipophilic, hydrophobic
PHBP221 8
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
The choice of salt form for a drug depends on The ability of a drug to exist in more than
the desired physical, chemical, or one crystalline form
pharmacologic proper ties. Amorphous, or non-crystalline, forms of a
drug have faster dissolution rates than do
Example: Chloramphenicol
crystalline forms.
Primary purpose: to increase the drug's water Amorphous/ non-crystalline solid:
solubility, increase absorption rate irregular shape
Drugs: weak acid + base = salt Crystalline solid: definite structure and
Drugs: weak base + acid = salt shape, particles are arranged in a
Weakly acidic drugs: potassium and sodium pattern
salts Polymorphs
Losartan Potassium - Same chemical structure
- Different physical properties: solubility, melting
Phenytoin Sodium
point, x-ray diffraction (ability of a crystal to
Sodium Ascorbate: sodium salt of ascorbic
scatter x-ray)
acid
Example: cocoa butter, used as a
Weakly basic drugs: hydrochloride, sulfate,
suppository base
citrate, gluconate salts, estolate, napsylate, - Alpha: melting point 22°C
and stearate salts - Beta prime: 28°C
Diphenhydramine hydrochloric acid (HCl) - Beta stable: 34.5°C, used as a
Morphine sulfate suppository base
Dextromethorphan hydrobromic acid (HBr) - Gamma: 18°C
Note: salts of long chain organic / fatty acids
G. Chirality
are non-polar (estolate, stearate, palmitate)
Example: Chloramphenicol palmitate: the ability of a drug to exist as optically active
antibacterial agent (see Figure 1) stereoisomers or enantiomers
o palmitate -> oral salt form Enantiomers: non-superimposable mirror
o succinate -> more water-soluble salt images of a compound. Same chemical
(administered via IV) structure but different in orientation in 3
dimensional space
Palmitic acid: 16 carbon carboxylic acid
can express as "S" or "R", "levo" or "dextro"
Individual enantiomers may not have the
same pharmacokinetic and
pharmacodynamic activity.
PHBP221 9
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
For example, ibuprofen (anti- inflammatory For example: The chelate of tetracycline
drug) exists as the R- and S-enantiomers; only with calcium is less water soluble and is
the S-enantiomer is pharmacologically active. poorly absorbed.
For example: Warfarin: anticoagulant R- - Tetracycline: broad spectrum
warfarin: longer half-life (t½), less distributed, antibiotic. It is capable of forming
less potent (weak); S-warfarin: shorter t½, complex or chelate with calcium.
more distributed, more potent
H. Hydrates
I. Complex Formation
PHBP221 10
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 11
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
ø Most of the emergency drugs are ø Maximum amount of drug solution that
formulated as intravenous bolus injection can be administered = 1.5 mL – 2 mL
ø Ex. Naloxone – antidote for opioid toxicity ø Administered at an angle of 45°
or poisoning; used in life threatening ø Ex of drugs administered via SC: Insulin,
situations Heparin
ø Disadvantage: increase probability of ø Bioavailability is the same with IM injection
increase risk of toxicity ø Advantage: the fatty tissue; adipose tissue;
Intravenous infusion – refers to the gradual subcutaneous tissue can actually store
administration of a drug into the veins in which lipophilic drugs wherein they can act as
the drugs is usually administered at a storage depot or drug reservoir for the
controlled and constant rate. Mas malaking lipophilic drugs which are administered via
amount of fluid ang inaadminister dito. subcutaneous injection. These tissues can
ø Administered at an angle of 25° store the lipophilic drugs wherein they can
ø Ex. Parenteral nutrition, Electrolytes, anti- release it in a gradual and constant
cancer drugs manner. That can increase the duration of
ø Advantage: It is easier to adjust the plasma action of the drug.
concentration of the drug ø Disadvantage: only few drug solutions can
ø Preferred intravenous route if the drug is be administered. Only few blood supplies
irritating. received. Lesser blood supply low rate
ø Disadvantage: can cause phlebitis of absorption
ø Phlebitis – <inflammation of the veins= Intradermal injection – one of the most
Intramuscular injections – the drug is directly common parenteral route of administration;
injected to the muscles the drugs is being injected into the dermis or
ø Administered at an angle of 90° inner layer of the skin
ø Ex. Vaccines and Hormones ø Administered at an angle of 10° - 15°
ø Common sites of injection: ø Usually used for allergy testing
- Deltoid muscle Enteral routes of administration – the drugs are
- Gluteus muscle intended to be absorbed inside the
- Thigh muscles alimentary canal or gastrointestinal tract.
ø Bioavailability Sublingual – intended to be dissolved under
- Aqueous solution – rapid absorption the tongue
process Ex. Nitroglycerin – vasodilator that is used in
- Non-aqueous solution – slow the treatment of angina (a heart condition
absorption process that is characterized by an extreme pain
ø Easier to administer than intravenous because of decrease blood flow/supply in
injections heart)
ø It allows the administration of larger Buccal – intended to be dissolved inside the
volumes of drug solution compared to cheek pouch
subcutaneous injections Oral route - the most common and most
ø Maximum amount of drug solution that preferred route of administration; also
can be administered = 5 mL considered to be the safest, most convenient,
ø Disadvantage: painful and easiest route of administration.
Subcutaneous injections – the drug is being ø Disadvantage: undergo first pass effect
injected into the hypodermis (the fatty layer Rectal route – suitable route of administration
beneath the skin wherein it is mainly for patients who cannot swallow.
composed of adipose tissue) ø Preferred route if the drug is being
degraded by the gastric acid or intestinal
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Primarily composed of: polar tails. Only allow the passage of non-
Lipid polar or lipophilic molecules, and non-ionized
Protein or hydrophobic molecules
Major functions: ø Cholesterol – determines the rigidity or fluidity
Hold together the aqueous cell contents of cell membrane
(structure) - More cholesterol = more rigid and stiff ang
Separate cellular contents from the cell membrane
aqueous external fluid (barrier) - Less cholesterol = more fluid cell membrane
Control transport of substances in and out ø Proteins
of the cell (regulation) a. Integral protein – embedded within the
phospholipid bilayer.
Theories of Cell membrane
Ex. protein channels
Lipid bilayer or unit membrane theory b. Peripheral protein – embedded on the
surface of the phospholipid bilayer.
composed of two layers of phospholipids
Ex. receptors, cell surface markers
between two surface layers of proteins
cell membranes have 2 phospholipid layers
and 2 protein layers
Phospholipid
ø 1 polar head and 2 non-polar tails
- Polar head attract water: hydrophilic
Fluid mosaic model 3 components: phosphate, choline,
consists of globular protein embedded in a glycerol
dynamic fluid, lipid bilayer matrix - Non-polar tails repel water: hydrophobic
Proteins embedded in a phospholipid bilayer. Made up of fatty acids or long carbon
Called as fluid model because in this chain carboxylic acids
biological model the molecules are Bilayer
constantly moving ø 2 layers of phospholipids
Called mosaic because the cell membrane - The polar heads stay on the outside and
is composed of many and different kinds of the tails stay on the inside
small molecules
Consists of globular protein embedded in a
dynamic fluid, lipid bilayer matrix
Important components
PHBP221 14
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 15
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 16
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Fast process, faster than passive diffusion Carrier mediated: Facilitated Diffusion
Plays an important role in the renal and biliary Characteristics
secretion of many drugs and metabolites.
carrier-mediated transport system
along concentration gradient
moves from a region of high drug
concentration to a region of a low drug
concentration
does not require energy
saturable and structurally selective
shows competition kinetics for drugs of a
similar structure
PHBP221 17
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Transport protein
ø may form an open channel across the lipid
membrane of the cell
Drug transport across tight (narrow) junctions
between cells or transendothelial channels of
cells
<Solvent drag= – the solvent or aqueous
medium which carries the dissolved molecules
into the pores or narrow junctions between
the cells
Inner lining of pores may possess charges in
ø Example: Propanol (+) + Oleic acid (-) =
which if they have charges, they can attract
will form a neutral complex (non-polar
ions with opposite charges
molecule; can easily cross the cell
Can also allow the transport of small ions membrane if non-polar)
especially if the ion has an opposite charge to
ø Examples
the charge of pore lining
Quaternary ammonium compounds – R4N+
ø Examples
Sulfonic acids – RSO3H
Inorganic and organic electrolytes up to
150 to 400MW Vesicular Transport
Ions of opposite charge of pore lining
The process of engulfing particles or dissolved
Ionized sulfonamides – a type of synthetic
materials by the cell.
antimicrobial agent
Types of bulk transport which is a types of
transport in which it involves the transport of
large amount of substances or molecules.
Transport of molecules in and out of the
cell by forming or using vesicles
ø Vesicles – cell organelles which are
described as tiny sacs that transports
material within or outside the cell
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Absorption
Movement of substances form the
gastrointestinal tract to the bloodstream
is the entry of constituents from the lumen of
the gut into the body. May be considered as
the net results of both lumen-to-blood and
blood-to-lumen transport movements.
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Duodenum - most proximal part that - Because Jejunum has better absorption
connected to the stomach. site/characteristics compared to Ileum
Jejunum - It is the middle portion
Ileum - distal part. Terminal portion.
PHBP221 22
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
RECTUM
15 cm, ending the anus
Drug absorption in the Gastrointestinal Tract
Distal part of Large Intestine
Drug absorption is variable/erratic The most common transport mechanism
The drug absorption in Rectum is highly for the absorption of drugs would be
dependent on the positioning or placement passive diffusion
of the drug within the rectum Drugs may be absorbed by passive
diffusion from all parts of the alimentary
(3) THREE DIVISIONS OF RECTUM
canal including sublingual, buccal, GI, and
1. Upper Rectum rectal absorption.
For most drugs, the optimum site for drug
Vein present: Superior Rectal Vein – it drains into absorption after oral administration is the
the hepatic portal vein upper portion of the small intestine or
Drug passes through the liver, thus it duodenum region.
undergoes first pass effect, resulting the
lower bioavailability of a drug Gastrointestinal Motility
GI motility tends to move the drug through the
2. Middle Rectum
alimentary canal so that it may not stay at the
Vein present: Middle Rectal Vein – it drains absorption site.
directly into the inferior vena cava Refers to the contraction of the smooth
muscles of the Gastrointestinal tract
PHBP221 23
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
This is also a major factor that can affect the Directly proportional to Absorption Rate (ú
rate and extent of absorption of a drug GER, úABSORPTION) then (ùGER,
ùABSORPTION)
The transit time of the drug in the GI tract
depends upon: ùGET, ú GER, ú ABS úGET, ùGER, ùABS
Fatty meal Cold foods
ø Pharmacologic properties of the drug Hot meal Mild exercise
ø Type of dosage form Stress Motility
ø Various physiologic factors Lying on the left Lying on the right
Side Side
Physiologic movement of the drug within the Heavy exercise Standing position
Anti-motility
GI tract depends upon whether the
alimentary canal contains recently ingested
food or is in fasted or inter-digestive state. Anti-motility drugs – drugs that decrease the
fast GIT motility, fast movement of passage gastrointestinal motility by decreasing the
of drug in gastrointestinal tract contraction of the smooth muscles in GIT
if may laman yung GIT, it results to slower
Examples of drugs that can decrease GIT Motility
GIT motility
and Rate and resulting slower Absorption Process
Gastric Emptying Time (GET)
Antidiarrheal drugs
The time it takes the stomach to empty its - Diphenoxylate + Atropine (Lomotil)
contents - Loperamide (diatabs, Imodium)
Major factor that affects the rate of Anticholinergics
absorption - Hyoscine butylbromide (buscopan)
Duodenum --- has the greatest capacity Opiates
for the absorption of drugs from the GI - Morphine + Codeine
tract
a delay in the gastric emptying time for *** HINDI PWEDENG PAGSABAYIN INUMIN YUNG
the drug to reach the duodenum will slow MGA DRUG NA YAN galet na qu emz
the rate and possibly the extent of drug Examples of drugs that can increase GER, reduce
absorption, hereby prolonging the onset GET and resulting Fast Absorption
time for the drugs.
(Motility enhancing drugs)
*** the longer it takes for the drug to reach the
duodenum, that would result to a slower rate of Antiemetic drugs
absorption of the drug - Metoclopramide
- Domperidone (Motilium)
*** If there is a delay in Gastric Emptying time,
that would also result to a delay in the drug Metoclopramide + Domperidone + other drugs =
absorption process increase rate of absorption of the other drugs
PHBP221 24
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Double-peak Phenomenon
The double-peak phenomenon is generally
observed after the administration of a single
dose to fasted patients
Food can also affect the integrity of the
dosage form causing an alteration in the
release rate of the drug
The rationale for the double-peak
phenomenon has been attributed to
variability in stomach emptying, intestinal
motility, presence of food, enterohepatic
recycling, or failure of a tablet dosage form.
Usually observed after the administration of a
single dose to a fasted patient
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Phase 1 Metabolism
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
ø During pregnancy
glucoronidation is reduced probably due
to increase progesterone and
pregnanediol levels
progesterone and pregnanediol levels –
considered as inhibitors of glucuronyl
transferase
ú rate of elimination = ù plasma
concentration = ù risk of toxicity
ø Newborns
very low glucuronyl transferase activity
Gray baby syndrome
kernicterus
Glucuronide – metabolite or product of a
glucuronidation reaction Gray Baby Syndrome and Kernicterus
Alcohols and phenols ether type
glucuronides
aromatic and aliphatic carboxylic acids
ester type glucuronides
PHBP221 33
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Acetylation
PHBP221 34
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 35
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Enzyme Induction
PHBP221 36
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
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Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
Excretion
Kidney
PHBP221 38
Biopharmaceutics and Pharmacokinetics
1ST SEMESTER – PRELIM
PHBP221 39