1

Pictured Pharmacology

Copyright: Katsuaki ItoVeterinary PharmacologyUniversity of Miyazaki

itokt@cc.miyazaki-u.ac.jp

2

per os (p.o.)

intravenous (i.y.)100

intraperitoneal (i.p.)IV

subcutaneous (s.c.)IVIMIP

intramuscular (i.m.)SC

3

4

404

P

PP

5

pH

pHpH

-

- - - -

+ + ++ +++

- -

pHpHHenderson-Hasselbalch

6

Henderson-Hasselbalch

pKa Ka=10-x MpKa=x

][]][[

HAAHKa+

=

loglog == pKapH

loglog == pKapH

pHpH

KaKapKapKapHHenderson-HasselbalchpKa6.5pH6.5

pKbpKb = 14 pKaHenderson-HasselbalchpKa

7

COO- COOH

9910.199.979010199650501090510905050419990103

0.199.99912

(pKa 5.0)(pKa 4.0)

pHNH3

+ NH2

(pKa 4.0)(pKa 5.0)pHHenderson-Hasselbalch

9

pH 2.4

pKa 9.4

74.94.2log === pKapH

10,000,0001

(pKa 9.4)3

pH2.4Henderson-Hasselbalch10-710,000,0001

8

pKapH

0

50

100

-4 -3 -2 -1 0 1 2 3 4

pH - pKa

pH pH

Copyright Katsuaki Ito, Miyazaki Univ.

pH pKapHpH

10

pH 8.4

pKa 9.4

14.94.8log === pKapH

101

100 1

pH8.481011/101/10pH7.4100

11

pKa 9.4

14.94.8log === pKapH

101

100 1

pH 8.4

1/10

12

pHpH6.66.6~6.9)~6.9)pH (7.4)pH (7.4)

QQ

log= pKapH

13

(pore) 40 4

P

P

Na,K-ATPaseCa-ATPaseH,K-ATPase

14

(first pass effect)

15

500~800 M 1 15~30 M

99%

90

1111/60 1

90

16

blood brain barrier (BBB)

BBB

P

(Bllod brain barrier: BBB)P

17

PP-glycoprotein

P

ATP ADPATP ADP

PP

18

P450CYP

P450 (CYP)UDP

20

P450 (CYP)

NADPH 6 CO450nm

-OH-

prodrug

p.26 p.16Copyright Katsuaki Ito, Miyazaki Univ.

21

**R*CYP1A2

********R**

CYP3A4

***

CYP2D6

***CYP2C19

R*S*

CYP2C9

*

450

****

P-

*

N-

*

22

CYP2A62C192C8/9/18, 3A4/5/7mRNA

CYP3A4

CYP

23

CYP1A2CYP2C9CYP1A2CYP1A2 2C9 2C193A4CYP1A2

CYP2C9CYP3A4CYP1A2 2C9, 3A4CYP2D6, PPCYP2C9PCYP1A2 2C9 2C193A4PCYP2C9CYP2C9CYP2D6CYP2E1

Nature Review 1:392002

CYP3A4

Grapefruit juice effect

24

conjugation

transferase

UDP

UDP

25

enterohepatic circulation

26

1)

2)

3) Henderson-HasselbalchpHpH

27

pH 6.4

pKa 9.4

10001loglog34.94.6 ====

pKapH

pH 7.4

pKa 9.4pH6.48.4

101loglog14.94.8 ====

pKapH

pH 8.4

pKa 9.4

pH 7.4

1001log24.94.7 ====

pKapH

pH6.48.4

28

60gpH8.57.5

55:219 2002)

log= pKapH

pHHenderson-HasselbalchpKapH PP450 (CYP)