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].