Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 1 PRINCIPLES OF CLINICAL PHARMACOLOGY
Take history, examine patient
and gather other data as
appropriate.
Make diagnosis.
Define therapeutic objective(s)
and develop therapeutic plan
(drug and/or non-drug
measures)
Non-drug measures:
supportive, management,
nutrition, environment
Modify therapeutic
objective/plan
Select drug and dosage
regimen.
Modify diagnosis
Monitor and evaluate response
to treatment
Change drug or
modify regimen
Continue treatment
Stop treatment
Fig. 1.1 Steps in the initiation, management and reassessment of drug therapy.
● Pharmacokinetics is the study of the characteristics
of the time course and extent of drug exposure in
individuals and populations and deals with the
absorption, distribution, metabolism and excretion
(ADME) of drugs. Pharmacokinetics has been
described as ‘what the body does to the drug’. Important
pharmacokinetic terms are briefly described
below and are discussed more comprehensively in
Chapter 2.
– Volume of distribution (V) is the constant that
relates the amount of drug in the body (A) to the
plasma drug concentration (C) (i.e. V = A/C), but
does not necessarily correspond to any actual
anatomic volume or compartment. V is a characteristic
of a drug rather than of the biological
system, although it may change in the presence of
disease, pregnancy, obesity and other states. By
knowing the value of V, it is possible to calculate
the dose necessary to obtain a target plasma concentration
(i.e. A = V · C), which corresponds to
the loading dose. The greater the volume of distribution
of a drug, the higher the dose necessary
to achieve a desired concentration. Amongst the
antibibacterial drugs, β-lactams are ionized at
physiological pH and generally have a low V,
while macrolides are concentrated in cells and
have a high V.
– Clearance (Cl) describes the efficiency of irreversible
elimination of a drug from the body (principally
by the major organs of biotransformation
and elimination, the liver and kidney) and is
defined as the volume of blood cleared of drug
per unit time. Clearance determines the maintenance
dose rate required to achieve a target
plasma concentration at steady state, as at steady
state there is an equilibrium whereby the rate of
drug elimination is matched by the rate and extent
of drug absorption.
– First-pass effect is a type of drug clearance and
defined as the extent to which an enterally administered
drug is removed prior to reaching the
systemic circulation by prehepatic and hepatic
metabolism. First-pass effects are important as a
possible source of variability in clinical response
to a drug and in explaining a component of the
difference in response between parenteral and
enteral administration of the same drug.
– Half-life (t 1/2 ): is the time taken for the amount of
drug in the body (or the plasma concentration) to
fall by half. In most cases it is the elimination
2