PART 2 PHARMACOKINETICS

SINGLE ORAL DOSE

- If the drug is given in an oral dosage

form (tablet, capsule, susp.,) the drug is
generally absorbed by FIRST ORDER
KINETICS.
- Elimination of the drug also follows the
principles of first order kinetics.

SIGNIFICANCE OF PEAK PLASMA

CONCENTRATION

The peak plasma concentration:

- Is one of the parameters used to

determine the comparative
bioavailability and/or the
bioequivalence between two products
(same or different dosage forms) but
containing the same chemical entity or
The peak time can be used: therapeutic agent
- To determine comparative o BIOEQUIVALENCE:
bioavailability ▪ two products
- To determine the preferred route of formulated from two
drug administration and the desired companies has the
dosage form for the patient same strength, dosage
- To assess the onset of action form, salt form (if there
is).
▪ Test of bioavailability
between two products
▪ Not bioequivalent if
not same dosage form,
strength, salt form.
- May be used to determine the
superiority between two different
dosage forms or two different routes of
administration
o Since there are different routes,
it will exhibit different peak
plasma concentration.
- May correlate with the pharmacological
effect of a drug
o If the cmax reached at a lower
period of time, the
pharmacologic effect will be felt
by the patient.
o If the cmax is high,
pharmacologic effect is also
high.
INTRAVENOUS INFUSION
- IV infusion allows precise control of
plasma drug concentrations to fit the
individual needs of the patient.
- It is an example of zero-order
absorption and first-order elimination.
- The plasma drug concentration at any
time after the start of an IV infusion is
given by the ff. equation:
𝑅
𝐶𝑝 = (1 − 𝑒 −𝑘𝑡 )
𝑉𝑑 𝑘
R= the zero-order rate of infusion given
in units as the milligram per hour
(mg/hr) or milligram per minute
(mg/min).
- If the IV is discontinued, the plasma
drug concentration declines by a first-
order process. The elimination half-life
or elimination rate constant, k, may be
obtained from the declining plasma
drug concentration versus time curve.
- As the drug is infused, the plasma drug
concentration increases to a plateau, or
steady-state concentration (𝐶𝑠𝑠 ).
o Under steady-state conditions,
the fraction of drug absorbed
equals the fraction of drug
eliminated from the body.
o The plasma concentration at
steady stae is given by the ff.
equation:
LOADING DOSE FORMULA:
INTERMITTENT IV INFUSION

a.) Intermittent IV infusions are infusions

in which the drug is infused for short
periods to prevent accumulation and
toxicity.
b.) It is used for a few drugs, such as the
aminoglycosides. For example,
gentamicin may be given as a 1-hr
infusion every 12 hrs. In thiscase,
steady-state drug concentrations are
not achieved.
 - When a multiple dose regimen is
designed, only the dosing rate (𝑫𝟎 /𝑻)
can be adjusted easily.
o The dose rate is based on the
size of the dose(𝑫𝟎 ) and the
interval (T) between doses, or
te frequency of dosing.
o The dosing rate is given by the
ff. equation:
𝑫𝟎
𝑫𝒐𝒔𝒊𝒏𝒈 𝒓𝒂𝒕𝒆 =
𝑻
o As long as the dosing rate is the
same, the expected average
drug concentration at steady
∞
state (𝐶min ) is the same.

MULTIPLE DOSES

- Many drugs are given intermittently in a

multiple-dose regimen for continuous
or prolonged therapeutic activity. This
regimen is often used to treat chronic
disease.
o If drug doses are given
frequently before the previous
dose is completely eliminated,
then plasma drug
concentrations accumulate and
increase to a steady-state
level.
- At steady state, plasma drug
concentration fluctuates between a
maximum and a minimum value.
- When a multiple dose regimen is
calculated, the superposition principle
assumes that previous drug doses have
no effect on subsequent doses. Thus,
the predicted plasma drug
concentration is the total plasma drug
concentration obtained by adding the
residual drug concentrations found
after each previous dose.