Immunosuppresive Drugs Commonly Used in Transplantation Models


Donor strain (heart)

Recipient strain

Tacrolimus dose (mg/kg)

The mean graft survival (days)

Administration of the drug

References

Brown-Norway

RT1n

Lewis

RT1I

1

10–15

Oral

Deuse et al. [13]

Brown-Norway

RT1n

Lewis

RT1I

2

15–20

Oral

Deuse et al. [13]

Brown-Norway

RT1n

Lewis

RT1I

8

20–25

Oral

Deuse et al. [13]

Brown-Norway

RT1n

Lewis

RT1I

0.3

7.8

Oral

Kinugasa et al. [14]

Brown-Norway

RT1n

Lewis

RT1I

0.6

9.8

Oral

Kinugasa et al. [14]

Lewis

RT1I

Lewis

RT1I

0.7

17

Oral

Kinugasa et al. [14]

ACI

Lewis

RT1I

0.032

16

Intramuscular

Fang [15]

F344 (RTAIvl)

Lewis

RT1I

0.025

11

Intramuscular

Li et al. [16]

F344(RTAIvl)

Lewis

RT1I

0.05

13

Intramuscular

Li et al. [16]

F344(RTAIvl)

Lewis

RT1I

0.1

52

Intramuscular

Li et al. [16]

Lewis

RT1I

Lewis

RT1I

0.2

40

Intramuscular

Jeske [17]

DA RT1avI

PVG RT1c

2.4

13

Oral

Qi et al. [18]

DA RT1avI

PVG RT1c

4.8

18

Oral

Qi et al. [18]












































































Donor strain (islet)

Recipient strain

Tacrolimus mg/kg dose

The mean graft survival (days)

Administration of the drug

References

ACI

RT1a

Lewis

RT1l

5

30

Intramuscular

Rastellini [19]

ACI

RT1a

Lewis

RT1l

10

30

Intramuscular

Rastellini [19]

Wistar

ACI

RT1a

1

71

Intramuscular
 

WKA

RT1u (renal subcapsular grafts)

Lewis

RT1l

0.32

13

Intramuscular

Yasunami [20]

WKA

RT1u (renal subcapsular grafts)

Lewis

RT1l

1

20

Intramuscular

Yasunami [20]

WKA

RT1u (intrahepatic grafts)

Lewis

RT1l

0.1

7

Intramuscular

Yasunami [20]

WKA

RT1u (Intrahepatic grafts)

Lewis

RT1l

0.32

42

Intramuscular

Yasunami [20]

WKA

RT1u (intrahepatic grafts)

Lewis

RT1l

1

45

Intramuscular

Yasunami [20]


























Donor strain (lung)

Recipient strain

Tacrolimus dose

The mean graft survival (days)

Administration of the drug

References

Brown-Norway RT1n

Lewis

RT1l

3 mg/kg

8.7

Intramuscular

Misao [21]


























Donor strain (pancreas)

Recipient strain

Tacrolimus dose

The mean graft survival (days)

Administration of the drug

References

DA RT1avl

Lewis RT1l

1 mg/kg

16

Intramuscular

Sakuma [22]















































Donor strain (kidney)

Recipient strain

Tacrolimus dose

The mean graft survival (days)

Administration of the drug

References

Brown-Norway RT1n

Lewis

RT1l

0.32 mg/kg

10

Oral

Jiang et al. [23]

Brown-Norway RT1n

Lewis

RT1l

1 mg/kg

23

Oral

Jiang et al. [23]

Brown-Norway RT1n

Lewis

RT1l

3.2 mg/kg

More than 100

Oral

Jiang et al. [23]

WKAH

Lewis

RT1l

5 mg/kg

68 (tacro administered 4,5,6 poTx days)

Oral

Hayakawa et al. [24]





3.3 Mycophenolate Mofetil/Sodium



3.3.1 Mechanism of Action


Mycophenolic acid is a fermentation product of Penicillium species that effectively blocks purine synthesis through allosteric inhibition of inosine monophosphate dehydrogenase. Purine nucleotides are synthetized by two pathways. The primary one is a de novo synthesis of inosinemonophosphate (IMP) from PPRP. The IMP is then used for synthesis of adenosine and guanosine by inosinemonophosphate dehydrogenase and adenosine deaminase, respectively. The second pathway for synthesis of purine nucleotides is their recyclation from guanosine and adenosine mediated by hypoxanthine guanine phosphoribosyltransferase and adenosine deaminase. Both pathways used PRPP.

The amount of PRPP in T and B lymphocytes is significantly increased after antigenic stimulation of the cells and is proven to be an important step before cell proliferation. Adding mycophenolic acid into the mixed lymphocyte reaction has effectively inhibited cell proliferation. Analyzing the cells by flow cytometry proved that lymphocyte passed through the G1 phase and stopped their mitosis in the S-phase. Another mechanism of action included depletion of GTP that may result in inhibition of G-protein based transduction signals. In immunized rats , the GTP pool significantly decreased after 4 days treatment with 20 mg/kg of MPA. MPA was shown to have a unique dual activity, both immunosuppressive and antimicrobial. Rats infected with Pneumocystis carinii did not develop pneumonia if they were treated with MPA [25].

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Sep 17, 2016 | Posted by in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off on Immunosuppresive Drugs Commonly Used in Transplantation Models

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