OLEH:

Diah Ramadhani., M.Si., Apt.

Pharmacokinetics Principles
 Absorption
 Distribution
 Elimination
 Dosage regimens
FACTORS AFFECTING ORAL DRUG
ABSORPTION:
 Transport
* Active vs. Passive
 Particle size
 Gastric emptying time
 pH
 Physical factors
* Blood flow
* Surface area
* Contact time
 Food
Effect of pH on absorption of a drug :
HA ------ H+ + A- --------- Acid
BH+ ------ H+ + B ---------- Base

Non-ionized forms like HA and B are lipid

soluble and cross the cell membrane.
Ionized forms like A- and BH+ are water
soluble and do not cross the membrane.
HENDERSON-HESSELBACH
EQUATION:

Effect of pH on ionization of weak acid:

HA ------------ H+ + A- ------ Acid

pH – pKa = log { A- or ionized}

---------------------------
{ HA or unionized}
HENDERSON-HESSELBACH EQUATION:

Effect of pH on ionization of weak base:

BH+ -------- B + H+ ----------- Base

pH – pKa = log { B / unionized}

------------------------------
{ BH+ / ionized }
Effect of pH on ionization of a drug

Weak acids become highly ionized as pH

increases,
Weak bases become highly ionized as pH
decreases.
pH and ionization
Acidic drugs are best absorbed in
Acidic medium

Basic drugs are best absorbed in Basic

medium
Bioavailability of a drug
 The bioavailability of a drug (by a route
other than intravenous) is given by:

AUC (extra vascular)

 F= -----------------------------
AUC (intravenous)
 Amount of drug absorbed or reaching
plasma = F x Dose
 For example the oral bioavailability (F) of
digoxin (lanoxin) is 0.7
 For digoxin 250 ug given orally, the effective or
absorbed dose = 0.7 x 250 ug
= 175 ug
Bioavailability of a drug:

Oral dose = Intravenous dose / F

• For example, the oral bioavailability of
theophylline is close to complete (F =1) so
that oral and intravenous dose rates are about
the same.
• Morphine has an oral bioavailability of about
0.2, so to achieve similar plasma
concentrations as intravenous, oral dose rates
need to be 5 times intravenous dose
(intravenous dose / 0.2).
BIOEQUIVALENCE: For two drugs to be bioequivalent, they
must have the same bioavailability and the same plasma
profile, i.e. the curve must have the same shape.
They must have the same Cmax and Tmax.
Cmax: The maximum plasma concentration attained by a
drug-administration.
Tmax: The time at which maximum concentration is reached.