PK/PD

Applications in
Antimicrobial
Phamacotherapy


Pharmacokinetics
(Dosage
regimen)

(Pharmacokinetics Parameters)

1. Beta Lactams
- Penicillins

- Cephalosporins
- Carbapenems : imipenem , meropenem
- Beta lactam / Beta lactamase inhibitors
(BLBI s) :
: Amoxicillin + Clavulanic acid
: Piperacillin + Tazobactam
: Cefoperazone + Sulbactam

 Penicillins .

Natural penicillin

Penicillin G
Benzathine penicillin

Penicillin V

Penicillin resistant
penicillin

Cloxacillin

Dicloxacillin

Aminopenicillin

Ampicillin

Amoxicillin

 Cephalosporins
.

Cefazolin

Cephalexin

2
3

Cefoxitin
Cefotaxime

Cefaclor
Cefdinir

Ceftriaxone
4

Ceftazidime
Cefpirom

2. Macrolides

- erythromycin - roxithromycin
- clarithromycin - azithromycin
3. Aminoglycosides
- gentamicin

- amikacin

- streptomycin
4. Floroquinolone
- norfloxacin
- ciprofloxacin

- ofloxacin

)
5. Lincosamides
6.
7.
8.
9.

- lincomycin
- clindamycin
Tetracyclines
- tetracyclines
- doxycycline
Sulfonamides
- sulfadiazine
- sulfamethoxazole
Polypeptides
- polymyxin B
- colistin
- vancomycin
Chloramphenicol


Pharmacokinetics (PK)

Pharmacodymamics (PD)

PK / PD


.


PK / PD


MIC

Pharmacokineti
cs

Pharmacokinetic
Processes

1. Absorption

2. Distribution
3. Metabolism or
Biotransformation

4. Excretion ,

Pharmacological Activity
Drug Absorption
Site of
therapeutic Effect Distribution in to Blood Cells

Site for Side Effects

Free Drug in Plasma

and Extracellular Fluid

Distribution to tis

Bound to plasma
Proteins

Toxicologic Activity

Biotransformation
to Metabolites

Reabsorpt

Excretory Sites

Excretion of
Unchanged Drug

Excretion of
Metabolites

Removal

1. Absorption

Mechanism of absorption

(lipid
bilayer)

High lipid solubility

Small size, Non-ionized

Onset =

Cmax =
Tmax =

Therapeutic effect

Concentration

Single Oral Dosing

MSC
(Maximum safety conc.)
Cmax
MEC
(Minimum effective conc.)

Time
Onset Tmax
Duration

Bioavailability,
F

The rate of absorption and the

extent of drug absorbed is avail
able in systemic circulation.

Value : 0-1 or 0- 100%

IV administration: F = 1 or
100%

2.Distribution
Blood circulation to site of action
Early phase: few minutes to
well-perfused organs: heart, liver
, renal, brain
Late phase: several minutes to
hours: muscle, visceral organs, sk
in, adipose tissue

Factors influencing
distribution

1) Physicochemical properties of dru

g
Size
Lipid solubility
2) Protein binding
Plasma protein binding
Tissue protein binding
3) Physiologic barrier

Physiologic barrier
Blood brain barrier (BBB): highly
lipophilic Phenobarbital
--> CNS
Placental barrier: highly
lipophilic, unionized form

 Pharmacokinetic

Absorption ()

- bioavailability

Distribution ()

- Volume of distribution

 Pharmacokinetic

Metabolism ()

- (Drug Interaction)

-

Excretion ()

-
-

Pharmacodynam
ics

Minimum inhibitor
concentration (MIC)

 PK / PD
1. Concentration dependent Killing activity

Aminoglycosides,
Fluoroquinolones
Metronidazole ,
Colistin
: C max / MIC = 10

 PK / PD
2. Time-dependent Killing Activity

. MIC
Beta-lactams , Macrolides
, Glycopeptides,
Clindamycin
T > MIC = 2 4

 PK / PD
2
1. 3-4 drip 15-30
6-8
2. loading dose continuous
infusion dirp

-
MIC4 dirp 3
24

Pharmacokinetic
parameters and Clinical p
harmacokinetics

1. Pharmacokinetic parameters

1) (Volume of distribution, Vd
2) (Clearance, CL)

3) (Half-life, t1/2 )

4) (elimination constant, ke

1)

(Volume of distribution, Vd)

Vd = Dose / Plasma drug concentration (Cp)

plasma
Vd
plasma/ tissue protein binding, affinity
of binding
Loading dose = Target Cp / Vd

Volume of distribution

Blood
Tissue

Vd

Vd =

dose
Plasma conc

High Protein Binding

Blood

Vd

Tissue

Protein binding
Vd

Tissue

Low Protein Binding

Blood

Tissue
Protein binding

Vd

Vd

Tissue

2) (Clearance,
CL)

/
CL = Drug excretion rate / Average plasma
drug concentration

Clearance: Total body clearance, Renal
clearance, Non-renal clearance
Maintenance dose
Dosing rate = CL x Target Cp, ss

3)
(Half-life, t1/2 )

(Dosing interval)

4-5 t1/2
steady state

4)
(elimination constant, ke)

hr-1

t1/2 = 0.693
ke

 (Duration)
(Steady-state)
(Loading dose)
(Maintenance dose)

Steady-state

Loading dose

Maintenace dose

steady-state

Concentration

Continuous IV infusion
MSC
Css
MEC

Time

Concentration

Multiple Dosing
MSC

MEC
Steady-state
Time

1.
2.
3.


1.


2.

Pharmacokinetics


3.

3.1
/ /
3.2
* Sulfonamide tetracycline

4
* Sulfonamide
G6PD


3.3
G6PD
Chloramphenicol , Sulfonamide , Primaquin

3.4
3.5

Fibrin Protein

Sulfonamide , Vancomycin


3.6
-
-

-