BIOPHARMACEUTICS AND PHARMACOKINETICS
Assignment No. 1
The LADMER System
In order to design a rational dosage regimen, a pharmacist must be familiar with the
concepts of the LADMER system (Liberation, Absorption, Distribution, Metabolism, Excretion
and Response). With the principles of this complex system on hand, one can make a suitable
treatment routine for a specific patient or group of patients with altered physiologic states.
1. Select one particular drug of interest. Illustrate a schematic diagram showing the LADMER
system that the selected drug undertakes inside the body. Specify the processes which the drug
goes through in each step of the complex LADMER system and the factors affecting these
processes. You may use product inserts and books as your reference.
BIOPHARMACEUTICS AND PHARMACOKINETICS
References
Aurobindo Pharma - Milpharm Ltd. (2020). Amoxicillin 500mg Capsules. Retrieved September
12, 2021, from https://www.medicines.org.uk/emc/product/526/smpc#gref
DrugBank.
(2021).
Amoxicillin.
Retrieved
September
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2021,
from
https://go.drugbank.com/drugs/DB01060
European Patients' Academy on Therapeutic Innovation. (2021). Drug Distribution. Retrieved
September 12, 2021, from https://toolbox.eupati.eu/glossary/drug-distribution/
BIOPHARMACEUTICS AND PHARMACOKINETICS
2. What are the pharmacotechnical factors affecting drug liberation? Discuss the significance of
liberation in drug’s bioavailability.
As stated by Smith (2019), drug liberation occurs when the formulation releases the
pharmaceutical substance responsible for the therapeutic action. This process is applicable for
medications taken orally because it requires drug disintegration and dissolution before being
absorbed. The main variables influencing the liberation of a drug are the physicochemical
properties of the drug, dosage form, and route of administration. First, the chemical nature of
the pharmaceutical substance serves as the basis of the rate and extent of drug absorption.
Hence, the drug’s solubility in water or lipid and its stability in an acidic environment alters the
liberation process. Moreover, the dosage form and route of administration on the basis of
permeability and surface area also affects liberation by declining the drug’s bioavailability as it
undergoes disintegration and dissolution.
References
Davis,
K.
(2021).
Pharmacokinetics.
Retrieved
September
12,
2021,
from
https://www.aacc.org/science-and-research/clinical-chemistry-trainee-council/traineecouncil-in-english/pearls-of-laboratory-medicine/2021/pharmacokinetics
Smith, Y. (2019). Pharmacokinetics. Retrieved September 12, 2021, from https://www.newsmedical.net/health/Pharmacokinetics.aspx
The Royal Society of Chemistry. (n.d.). Pharmacokinetic processes: liberation. Retrieved
September 12, 2021, from https://edu.rsc.org/download?ac=12816
3. Give at least three (3) dosage forms in which liberation is altered?
According to the United States Food and Drug Administration (2019), parenteral
administration refers to the non-oral drug administration preferably given to achieve high
therapeutic concentrations and bioavailability. Dosage forms that are administered by means of
a parenteral route of administration, such as intravenous (injected into the vein),
subcutaneous (injected into the loose subcutaneous tissue), and intramuscular (injected to
muscle), do not undergo the process of liberation wherein the drug must be disintegrated and
converted into a solution. It is due to the fact that the pharmaceutical substances delivered in
these dosage forms are already in their solution form.
Furthermore, as for the peroral route of administration, sublingual (administered under
the tongue) and buccal (administered between the cheek and gum) is effective in making sure
that the drug’s onset of action is immediate. In accordance with the specified dosage forms, the
liberation process is altered because medications are directly absorbed by the blood vessels
found under the tongue or in the lining of the mouth.
References
Jones & Bartlett Learning Publishers, Inc. (n.d.). Dosage Forms, Routes of Administration, and
Dispensing
Medications.
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BIOPHARMACEUTICS AND PHARMACOKINETICS
Kohrs, N., Liyanage, T., Venkatesan, N., Najarzadeh, A., & Puleo, D. (2019). Drug Delivery
Systems and Controlled Release. Encyclopedia of Biomedical Engineering, 316-329. doi:
10.1016/b978-0-12-801238-3.11037-2
Pawar, A. (2020). Sterile/Parenteral Dosage Forms. Retrieved September 11, 2021, from
http://www.mespharmacy.org/wp-content/uploads/2020/06/Parenteral-dosage-formIntroduction.pdf
4. Define the following terms:
a. Absorption
In pharmaceutical parameters, absorption is defined as the movement of the drug
from the route of administration to the bloodstream. Before penetrating the systemic
circulation, this process depends on several underlying procedures such as passive
diffusion, facilitated diffusion, active transport, and endocytosis (Paul, 2019). Furthermore,
the efficacy of absorption depends on the properties of the drug (e.g. solubility) and the
pH of its surroundings. In addition, absorption is also affected by several factors such as
the formulation of drugs (e.g. capsules, lozenges, liniments, ointments), site of drug
administration (e.g. oral, parenteral, topical), and gastric emptying rate (GER).
References
Paul, A. (2019). Drug Absorption and Bioavailability. Retrieved September 10, 2021, from
https://link.springer.com/chapter/10.1007/978-981-32-9779-1_5
International Union of Basic and Clinical Pharmacology. (n.d.). Drug Absorption. Retrieved
September
10,
2021,
from
https://www.pharmacologyeducation.org/pharmacology/drug-absorption
Smith, Y. (2019). What is Drug Absorption. Retrieved September 10, 2021, from
https://www.news-medical.net/health/What-is-Drug-Absorption.aspx
b. Bioavailability
In relation to the absorption process, bioavailability is the extent to which there is
an occurrence of absorption. It is expressed as the fraction of the active form of a drug
that successfully reaches the systemic circulation, specifically the site of action or the
drug’s intended target, considering that the initial dose of the drug is in its unchanged
form. However, factors like the route of drug administration (e.g. oral administration)
reduce the bioavailability due to the ‘first-pass effect’ of hepatic metabolism. In addition,
the topical route of administration reduces bioavailability because most drugs are poorly
lipid-soluble and contain high molar mass. Consequently, drugs are not absorbed entirely
via the mucous membrane.
References
Hinderliter, P., & Saghir, S. A. (2014). Pharmacokinetics. Encyclopedia of Toxicology
(Third Edition). doi: 10.1016/B978-0-12-386454-3.00419-X
BIOPHARMACEUTICS AND PHARMACOKINETICS
Patel, D., & Price, G. (2020). Drug Bioavailability. Retrieved September 10, 2021, from
https://www.ncbi.nlm.nih.gov/books/NBK557852/
Wolverton, S. (2021). 1 - Basic Principles of Pharmacology. Comprehensive Dermatologic
Drug Therapy (Fourth Edition). doi: 10.1016/B978-0-323-61211-1.00001-2
c. Disposition
According to the University of Auckland Department of Pharmacology and Clinical
Pharmacology (n.d.), disposition, from the term “dispose of”, refers to the process involved
in the occurrence of drug administration, specifically after the release of the drug from the
drug product. It includes underlying processes such as drug distribution and elimination
(metabolism and excretion). Disposition entails the distribution of drug from the systemic
circulation to the site of action, and biotransformation of the drug in order to proceed in the
elimination of the administered drug from the body.
References
Garza, A., Park, S., & Kocz, R. (2020). Drug Elimination. Retrieved September 10, 2021,
from https://www.ncbi.nlm.nih.gov/books/NBK547662/
Smith, Y. (2019). Drug Metabolism. Retrieved September 10, 2021, from
https://www.news-medical.net/health/Drug-Metabolism.aspx
The University of Auckland Department of Pharmacology and Clinical Pharmacology.
(n.d.). Absorption and Disposition. Retrieved September 10, 2021, from
http://holford.fmhs.auckland.ac.nz/teaching/medsci719/workshops/absorptionanddis
position/
Shargel, L., & Yu, A. (2016). Introduction to Biopharmaceutics and Pharmacokinetics.
Applied Biopharmaceutics and Pharmacokinetics (7th ed., pp. 1-4). Norwalk, Conn:
Appleton & Lange.
d. Volume of distribution
Mahabadi and Mansoor (2021) stated that volume of distribution (Vd) is a
pharmacokinetic parameter used to represent the capacity of a drug to either be circulated
to other tissues or remain in blood plasma. This theoretic concept signifies the
interrelationship between the dose of a drug in the body and the concentration measured
in blood plasma. In relation to that, the volume of distribution is calculated by dividing the
drug dose between the body and the plasma concentration.
Volume of distribution (L)=
amount of drug∈the body (mg)
plasma concentration(mg/ L)
Using the formula above, it can be determined whether there is more distribution to
other tissues (if the result shows high Vd) or less distribution to other compartments of the
body (if the result shows low Vd).
BIOPHARMACEUTICS AND PHARMACOKINETICS
References
Alsanosi, S., Padmanabhan, S., & Skiffington, C. (2014). Pharmacokinetic
Pharmacogenomics. Handbook of Pharmacogenomics and Stratified Medicine. doi:
10.1016/B978-0-12-386882-4.00017-7
Cladis, F., Davis, P., & Motoyama, E. (2011). Pharmacology of Pediatric Anesthesia.
Smith's Anesthesia for Infants and Children (8th ed.). doi: 10.1016/B978-0-32306612-9.00007-9
Mahabadi, N., & Mansoor, A. (2021). Volume of Distribution. Retrieved September 10,
2021, from https://www.ncbi.nlm.nih.gov/books/NBK545280/
e. Biliary recycling
Biliary recycling, also known as enterohepatic recirculation, refers to the process
where the drugs or metabolites undergo excretion in the biliary system. It happens when
the drugs from the liver pass through the bile, then stored in the gall bladder, and released
into the small intestine. After reaching the small intestine, the drug can be reabsorbed
from the distal intestinal lumen and eventually return to circulation and liver.
References
Gebhart, G., & Schimdt, R. (2013). Enterohepatic Recirculation (Biliary Recycling).
Retrieved September 11, 2021, from 10.1007/978-3-642-28753-4_200713
McGraw-Hill Concise Dictionary of Modern Medicine. (n.d.). Enterohepatic Recirculation.
Retrieved
September
11,
2021,
from
https://medicaldictionary.thefreedictionary.com/enterohepatic+recirculation
Andrews, K., Bolger, M., Clark, R., Grasela, T., Lukacova, V., & Morris, D. (2017). Human
PK Prediction and Modeling. Comprehensive Medicinal Chemistry III. doi:
10.1016/B978-0-12-409547-2.12373-X
f.
Excretion
Smith (2019) defined drug excretion as the final elimination of pharmaceutical
substances and/or their metabolites from the systemic circulation of the body. All drugs
are excreted either through metabolic biotransformation or in their unmetabolized form.
One factor that affects drug excretion is the size of body fluid compartments. This factor
varies from different age groups; hence, the probability of having alterations in the action
of particular drugs must be taken into consideration.
References
Barreto, E., Koubek, E., & Larson, T. (2021). Drug Excretion. Reference Module in
Biomedical Sciences. doi: 10.1016/B978-0-12-820472-6.99999-7
Brownstein, J. (2019). Fundamental Principles of Pediatric Physiology and Anatomy.
Pediatric Dentistry (6th ed.). doi: 10.1016/B978-0-323-60826-8.00006-7
BIOPHARMACEUTICS AND PHARMACOKINETICS
Divinagracia, M. (n.d.). Definition of Terms. Retrieved September 11, 2021, from
https://www.scribd.com/document/320727426/DEFINITION-OF-TERMS
Smith, Y. (2019). Drug Excretion/Elimination. Retrieved September 11, 2021, from
https://www.news-medical.net/health/Drug-Excretion-Elimination.aspx
g. Protein binding
Protein binding specifies the extent to which the total amount of a drug in plasma or
tissue attaches to plasma or tissue proteins. The drug’s efficacy and performance relate to
protein binding by either enhancing or detracting it. Several pharmaceutical substances
bind to plasma proteins, preventing the bound drug to pass through the membranes.
Consequently, pharmacologic actions of the drug are affected by the degree of protein
binding by changing the drug’s concentration or rate of drug elimination.
References
Davis, J. (2018). Pharmacologic Principles. Equine Internal Medicine, 79-137. doi:
10.1016/b978-0-323-44329-6.00002-4
Deb, P., Al-Attraqchi, O., Prasad, M., & Tekade, R. (2018). Protein and Tissue Binding.
Dosage Form Design Considerations, 371-399. doi: 10.1016/b978-0-12-8144237.00011-3
Kwon, Y. (n.d.). Protein Binding. Handbook of Essential Pharmacokinetics,
Pharmacodynamics and Drug Metabolism for Industrial Scientists (p. 105). doi:
10.1007/0-306-46820-4_7
Lalatsa, A., Schätzlein, A. & Uchegbu, I. (2011). Drug Delivery Across the Blood–Brain
Barrier. Comprehensive Biotechnology (2nd ed., Vol. 5, pp. 657-667). doi:
10.1016/B978-0-08-088504-9.00180-X
h. Enzyme inhibitor
As stated by Gibb and Roberts (2013), enzyme inhibitor refers to the substances
that act to decrease enzyme-related processes such as its production and actions. This
inhibitor binds to enzymes, causing the catalytic substance to lose its activity; however,
the protein structure of the enzyme remains undamaged. Furthermore, enzyme inhibitors
are known to take part in the process of drug discovery. Through the use of a suitable
enzyme inhibitor, the hyperactivation of enzymes involved aids in examining the disease
at the molecular level.
References
Ata, A. (2012). Novel Plant-Derived Biomedical Agents and Their Biosynthetic Origin.
Studies in Natural Products Chemistry (Vol. 38, pp 225-227). doi: 10.1016/B978-0444-59530-0.00008-3
Gibb, A., & Roberts, S. (2013). Introduction to enzymes, receptors and the action of small
molecule drugs. Introduction to Biological and Small Molecule Drug Research and
Development. doi: doi.org/10.1016/B978-0-12-397176-0.00001-7
BIOPHARMACEUTICS AND PHARMACOKINETICS
Gomes, A., & Santos, T. (2019). Bioassays | Enzyme Assays. Encyclopedia of Analytical
Science (3rd Edition). doi: 10.1016/B978-0-12-409547-2.14331-8
i.
Enzyme inducer
Kedderis (2018) defined enzyme inducers involves the process of increasing the
biosynthesis of catalytic enzymes due to specific stimuli. This process is necessary for the
mechanisms of chemical interactions due to the fact that an increase in the amount of
enzyme protein exposes the body to chemical agents. Hence, the rate of hepatic
metabolism also increases as the rate of enzymatic processes increases.
References
Merry, C., & Flexner, C. (2012). Pharmacology of antiretroviral drugs. Sande's HIV/AIDS
Medicine, 169-176. doi: 10.1016/b978-1-4557-0695-2.00013-4
Kedderis, G. (2018). Toxicokinetics: Biotransformation of Toxicants. Comprehensive
Toxicology, 128-142. doi: 10.1016/b978-0-12-801238-3.01888-2
Roskoski, R. (2007). Modulation of Enzyme Activity. Xpharm: The Comprehensive
Pharmacology Reference, 1-11. doi: 10.1016/b978-008055232-3.60042-x
j.
Extravascular administration
Extravascular administration takes place before the drug reaches the systemic
circulation. In clinical aspects, extravascular administration is safe, cost-effective, and
convenient. However, in cases where the drug is destroyed before being absorbed (e.g.
when the substance has poor digestive tolerability), extravascular administration is not
preferable. As a matter of fact, this type of drug administration limits the dose from being
fully absorbed. Furthermore, factors that must be taken into consideration in extravascular
drug delivery are metabolism, drug degradation, and patient differences in the aspect of
absorption rate.
References
Divinagracia, M. (2016). Biopharmaceutics Definition of Terms. Retrieved September 11,
2021, from https://www.scribd.com/document/320727426/DEFINITION-OF-TERMS
Godfrey, K. (n.d.). Pharmacokinetics. Retrieved September 11, 2021, from
https://journals.sagepub.com/doi/abs/10.1177/014233128200400405?
journalCode=tima
Shargel, L., & Yu, A. (2012). Introduction to Biopharmaceutics and Pharmacokinetics.
Applied Biopharmaceutics and Pharmacokinetics (6th ed.). Norwalk, Conn: Appleton
& Lange.
University of Lausanne. (n.d.). Extravascular Administration. Retrieved September 11,
2021, from https://sepia2.unil.ch/pharmacology/profiles/extravascular-administration/
BIOPHARMACEUTICS AND PHARMACOKINETICS
k. Intravascular administration
The United States Food and Drug Administration (2017) defined intravascular
administration as drug administration within the blood vessels. This type of administration
allows the drug to directly reach the systemic circulation. Intravascular administration is
effective in ensuring the high extent to which there is an occurrence of absorption; thus, it
increases the bioavailability of the pharmaceutical substance.
References
Shargel, L., & Yu, A. (2012). Introduction to Biopharmaceutics and Pharmacokinetics.
Applied Biopharmaceutics and Pharmacokinetics (6th ed.). Norwalk, Conn: Appleton
& Lange.
United States Food and Drug Administration. (2017). Route of Administration. Retrieved
September 11, 2021, from https://www.fda.gov/drugs/data-standards-manualmonographs/route-administration
l.
Pharmacokinetics
Pharmacokinetics, from the Greek words pharmakon (drug) and kinetikos
(movement), identifies what the body does to the drug (Nebert & Zhang, 2019). It is the
study of dynamic movements of administered drug substances in the body during a
certain period of time. Furthermore, Grogan and Preuss (2020) mentioned that this aspect
of pharmacology generally has four parameters - absorption, distribution, metabolism/
biotransformation, and excretion (ADME). By the use of mathematical equations and
models, pharmacokinetics depicts the extent of the therapeutic or toxic effects of drugs.
References
Delgoda, R., Gurley, B., Picking, D., & Turfus, S. (2017). Pharmacokinetics.
Pharmacognosy
Fundamentals,
Applications
and
Strategies.
doi:
https://doi.org/10.1016/B978-0-12-802104-0.00025-1
Grogan, S., & Preuss, C. (2020). Pharmacokinetics. Retrieved September 10, 2021, from
https://www.ncbi.nlm.nih.gov/books/NBK557744/
Hinderliter, P., & Saghir, S. A. (2014). Pharmacokinetics. Encyclopedia of Toxicology
(Third Edition). doi: https://doi.org/10.1016/B978-0-12-386454-3.00419-X
National Institutes of Health. (n.d.). Pharmacokinetics. Retrieved September 10, 2021,
from
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/
pharmacokinetics
Nebert, D., & Zhang, G. (2019). Pharmacogenomics. Emery and Rimoin's Principles and
Practice of Medical Genetics and Genomics (Seventh Edition). doi:
https://doi.org/10.1016/B978-0-12-812537-3.00016-0
BIOPHARMACEUTICS AND PHARMACOKINETICS
Shargel, L., & Yu, A. (2016). Introduction to Biopharmaceutics and Pharmacokinetics.
Applied Biopharmaceutics and Pharmacokinetics (7th ed., pp. 1-4). Norwalk, Conn:
Appleton & Lange.
m. Gastric emptying time
Lee (2021) defined gastric emptying time (GET) as the time interval spent from the
point of ingestion of the drug until it exits the stomach. In relation to that, an abrupt
temperature rise is evident during capsule ingestion, while an abrupt rise in acid level is
observed once the drug moves from the acidic gastric environment to a comparatively
basic duodenum. Peterson (2016) further discussed that during this duration of time,
acceleration and delay of the emptying process are dependent on the excitatory and
inhibitory nerves.
References
Jacoby, H. (2017). Gastric Emptying. Reference Module in Biomedical Sciences. doi:
10.1016/b978-0-12-801238-3.64921-8
Lee, A. (2021). The use of wireless motility capsule in the diagnosis and monitoring of
gastroparesis. Gastroparesis, 143-159. doi: 10.1016/b978-0-12-818586-5.00012-0
Peterson, J. (2016). Noninvasive In Vivo Optical Imaging Models for Safety and Toxicity
Testing. Nutraceuticals, 305-317. doi: 10.1016/b978-0-12-802147-7.00023-1
University of Pittsburgh Medical Center. (n.d.). Gastric Emptying Study. Retrieved
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%20gaining%20weight.
n. Prodrug
A prodrug refers to the medicinal compound used to enhance absorption,
distribution, metabolism, and elimination (ADME) rate by maintaining its state of being
inactive until it reaches the point of delivery and becomes an active pharmacologic agent.
Prodrug prevents the likelihood of decreasing the potency of a drug while it is being
transported. Furthermore, this chemical modification of biologically active substances
provides a means of preventing the occurrence of chemical instability, toxicity, local
irritation, and low solubility.
References
Ates-Alagoz, Z., & Adejare, A. (2021). Prodrugs. Remington, 169-186. doi: 10.1016/b9780-12-820007-0.00009-x
European Molecular Biology Laboratory. (2021). CHEBI:50266 – prodrug. Retrieved
September 11, 2021, from https://www.ebi.ac.uk/chebi/searchId.do?chebiId=50266
BIOPHARMACEUTICS AND PHARMACOKINETICS
Marks, J. (2021). Definition of Prodrug. Retrieved September 11, 2021, from
https://www.rxlist.com/prodrug/definition.htm
Workplace Testing Inc. (n.d.). Prodrug. Retrieved September 11, 2021, from
https://www.workplacetesting.com/definition/4299/prodrug
o. Pharmacodynamics
Pharmacodynamics, from the Greek words pharmakon (drug) and dynamikos
(power), determines what the drug does to the body (Braund, Peake, Tong, & Tremblay,
2016). It refers to the study of molecular, biochemical, and physiological actions of the
drug as it reaches the target biological structure. When a certain dose of medicine results
in a therapeutic response, the relationship between the concentration of the drug and the
physiological effect is specified. Furthermore, biochemical response or effect can be seen
when there is an interaction between the drug administered and the body’s drug-receptor.
References
Braund, R., Peake, B., Tong, A., & Tremblay, L. (2016). Prescribing practices. The LifeCycle of Pharmaceuticals in the Environment. doi: https://doi.org/10.1016/B978-1907568-25-1.00002-5
Hallworth, M. (2014). Therapeutic drug monitoring. Clinical Biochemistry: Metabolic and
Clinical Aspects (Third Edition). doi: https://doi.org/10.1016/B978-0-7020-51401.00039-0
Jamal, Z., Marino, M., & Zito, P. (2021). Pharmacodynamics. Retrieved September 11,
2021, from https://www.ncbi.nlm.nih.gov/books/NBK507791/
Shargel, L., & Yu, A. (2016). Introduction to Biopharmaceutics and Pharmacokinetics.
Applied Biopharmaceutics and Pharmacokinetics (7th ed., pp. 1-4). Norwalk, Conn:
Appleton & Lange.
p. Biopharmaceutics
Biopharmaceutics is derived from the term pharmaceutics (field of study dealing with
preparation, dispensing of medicine) and Greek term bios (life particularly living organisms
or tissues). From these two terms, biopharmaceutics can be defined as the science of
drug administration in living organisms or tissues. This study examines the drug’s
physicochemical properties, dosage form, and route of administration in relation to the
rate, intensity, and extent of drug action.
References
Amiji, M., Cook, T., & Mobley, W. (2014). Introduction to Biopharmaceutics. Applied
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BIOPHARMACEUTICS AND PHARMACOKINETICS
Barbour, N., & Lipper, R. (2008). Introduction to Biopharmaceutics and its Role in Drug
Development. Biopharmaceutics Applications in Drug Development (pp. 1-2). New
York, USA: Springer.
Duan, J., Yang, Y., Zhang, X., Zhao, L., Zhao, P., & Zhao, Y. (2017). Predictive
Biopharmaceutics and Pharmacokinetics: Modeling and Simulation. Developing
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