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Chap. 1 Pharmacokinetics
I. &

II.

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A. (Enteral)
1. (Oral):
z (stomach)
(duodenum) (ileum)

z
(hepatic portal circulation)
(first pass metabolism):

Nitrooglycerin 90%

2.(Sublingual):
z
z
z pH

3(Rectal):
z 50%

z pH
z

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B. (parenteral)
z
z (lnsulin)
z ()
z

1. (Intravenous, lV):
z
z

z
z
z (hemolysis)

2(lntramuscular IM):
z : (suspension)
(ethylene glycol)
(peanut oil)

:protamine-zinc insulin

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3(subcutaneous, sc):
z
z

C.
1.(Inhalation):
z

2(Topical):

z
z

3 (Transdermal):

:
(antimotion sickness) scopolamine
(antiaginal) nitroglycerin

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III ABSORPTION OF DRUGS

(Absorption):

(effciency)

=

(epithelial cells)

A.
(Transport of drug from the Gastrointestinal (GI) tract)
1. (Passive diffusion):
z
z
z
z (carrier)
z
z (aqueous channels)

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2 (Active transport):
z (carrier proteins)
z
z

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B. pH

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C.
1.
>
>
2.
(microvilli)
>
>
3.
Gastric Emptying

1.
: Tetracycline, Penicillin, Lincomycin, Rifampin
2. Tetracychne Tetracycline
3. Ketoconazole
4. Fat>protein>Carbohydrate()
5. Digoxin, Acetaminophen, Pentobarbital, Sulfonamide,
Cephalexin ()
6. griseofulvin

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IV (Bioavailability)

eg. 100mg 70mg 70%

A.
1. (First pass hepatic metaboIism):

10

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2:

3:
Penicillin G pH

4(Nature of drug formulation):

()

11

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B. (Bioequivalence)
(bioequivalent)
(bioinequivalent)

C. (Therapeutic equivalence)
(therapeutic
equivalence)
(effectiveness):

12

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V. (DRUG DISTRlBUTION)
()

13

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A. (Blood fIow)

(adipose tissue, )

B. (CapiIlary permeability)

1(Capillary structure):

2. (Blood-brain barrier)

-

(blood-brain
barrier)

14

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2(Drug structure):
z


z

15

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C. (Binding of drugs to proteins)

()

D.

(PCB)

Drug Metabolism
:
(1) &

(2) (detoxification)
:
1.
diazepam() nordiazepam oxazepam

16

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2. (prodrugs):

levodopa dopamine
3. cytochrome P-450
afflatoxin ()
O

O
O
O

OMe
O

OMe

Aflatoxin

O
N

NH

O
NH

OH

DNA
O
O

OMe

(Phase I metabolism)
(: -OH)

(oxidation)
-(mixed function oxidases)
cytochrome P-450

: (reductions)(hydrolysis)

17

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(Phase II metabolism)

(conjugation)

(enzyme induction)
cytochrome P-450

18

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A. (Renal elimination of drug)

1.(Glomerular filtration):

()
()
(GFR=125ml/min) (RPF = 600ml/min)
20%

2. (Proximal tubular secretion)

(carrier)

3(Distal tubular reabsorption):

>>
(osmosis)

pH
NH4Cl

19

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4. (Role of drug metabolism)

1. (hydroxyl group)

2. sulfate, glycine glucuronic acid

3.

20

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21