506522 - PHARMACOKINETICS AND THERAPEUTIC DRUG MONITORING
Current prerequisite courses are Chemistry, Biology, Biochemistry,
Anatomy and Physiology.
Basics of basic mathematics already used in chemistry and physics
courses. Students need to have some background in chemical kinetics,
i.e. zero and first order processes.
The learning objectives of the course are: 1) understand the meaning of
the primary pharmacokinetic parameters (distribution volume and
clearance, bioavailability) and secondary ones (elimination rate constant,
half-life, etc). 2) Determine primary and secondary pharmacokinetics
parameters from concentration-time data. 3) Understand the influence of
the route of administration and the various therapeutic regimens on the
plasma concentration-time profile and predict the effect on it of clearance
and distribution volume changes, and other specific patient
characteristics. 4) Understand the role of pharmacokinetic drug
monitoring in choosing the correct dosage regimen in each individual
Introduction to pharmacokinetics: absorption, distribution and elimination
(metabolism and excretion), disposition. Clinical pharmacokinetics,
pharmacodynamics, kinetic homogeneity, models. Exponents and
logarithms. Meaning of differential calculus, differential equations,
integral calculus. AUC determination by trapezoidal rule. Orders of
kinetic: first- and zero-order kinetics, Michaelis-Menten kinetic.
Pharmacokinetics models: one-compartment and multiple compartments
models. Non compartment model. Concentration-time curves, linear
plots, semi-log plots. i.v. (bolus) single dose administration.
Pharmacokinetic parameters associated with models and their
calculation: C0, volume of distribution, clearance, elimination rate
constant, half-life. Factors affecting drug distribution: characteristics of
drug, characteristics of barrier to be crossed, regional blood flow, drug
plasma and tissue protein binding, physiological factors and disease
states. Blood-brain barrier and placenta transfer of drugs. Clearance:
total plasma or blood clearance, organ clearance, extraction ratio. Well stirred
model of hepatic clearance, low and high hepatic extraction ratio
drugs, renal clearance. Bioavailability. Route and frequency of
administration: i.v. continuous constant rate infusion with and without
reaching steady state; extra vascular administration and related
parameters, single and multiple doses. Generic drugs, biotechnological
and biosimilar drugs. Therapeutic drug monitoring, definition. Therapeutic
ranges and reference ranges. TDM procedure, assay methods. Examples
of drugs monitored. Theoretical background needed to make clinically
useful TDM. Individual therapeutic concentration. Examples of drug with
Lectures carried out through presentations (PowerPoint) projected on the
screen and possible further information using the blackboard or with
other systems in relation to the COVID-19 emergency.
Laurence Brunton et al., Goodman and Gilman's The Pharmacological
Basis of Therapeutics, 13th Edition, New York McGraw-Hill, 2018.
Stephen H. Curry, Robin Whelpton, Introduction to Drug Disposition and
Pharmacokinetics 2017 John Wiley & Sons, Ltd.
Written examination consisting of multiple choice and open questions
primarily based on didactic material covereded in the course, regardless
of whether the examination is carried out in person or via the internet in
relation to the COVID-19 emergency. Graphics is emphasized: the student
must know how to draw plasma concentration - time curves, etc.
The lecturer will provide .pdf presentations and other study materials of
the topics discussed.
It is also available on request for explanations to groups or individual
students by appointment.
- Teacher: FAUSTO FELETTI