Title: Blood, cellular and tissular calcineurin inhibitors pharmacokinetic-pharmacodynamic relationship in heart transplant recipients: the INTRACAR study
Authors:
Mr. Gwendal Coste, M.Sc.; Dr. Céline Chabanne, M.D.; Dr. Camille Tron, PhamD., Ph.D.; Dr. Bernard Lelong, M.D.; Dr. Marie-Clémence Verdier, PharmD., Ph.D.; Pr. Mikael Roussel, PharmD., Ph.D.; Dr.
François Le Gall, M.D.; Dr. Bruno Turlin, M.D., Ph.D.; Dr. Mireille Desille-Dugast, Ph.D.; Pr. Erwan Flécher, M.D., Ph.D.; Pr. Bruno Laviolle, M.D., Ph.D.; Dr. Florian Lemaitre, PharmD., Ph.D.
*: Corresponding author. Email: [email protected]. Postal address: Laboratoire de pharmacologie biologique, Pôle biologie, CHU de Rennes, 2 rue Henri Le Guilloux, 35033 Rennes CEDEX 9, France. Telephone: 06.42.08.80.03
Supplementary figures
A: 03
50 100 150 200
0 1000 2000 3000 4000
0 100 200 300 400
Days since the graft
B: 07
200 250 300 350 400 450 500 0
200 400 600 800 1000
0 20 40 60 80 100
Days since the graft
C: 20
80 100 120 140 160 180
0 500 1000 1500 2000
120 140 160 180 200
Days since the graft
D: 22
80 100 120 140
0 500 1000 1500
120 140 160 180 200 220
Days since the graft
E: 23
0 100 200 300 400 500
0 1000 2000 3000 4000
0 100 200 300 400
Days since the graft
F: 24
150 200 250 300
0 200 400 600 800 1000
110 120 130 140 150 160
Days since the graft
G: 25
100 200 300 400
0 500 1000 1500 2000 2500
100 120 140 160 180 200
Days since the graft
H: 26
0 100 200 300 400
0 500 1000 1500 2000
0 50 100 150 200 250
Days since the graft
I: 27
150 200 250 300 350
0 500 1000 1500
150 200 250 300 350
Days since the graft
J: 29
100 150 200 250 300 350
0 200 400 600 800 1000
0 50 100 150 200 250
Days since the graft
K: 30
150 200 250 300 350
0 500 1000 1500 2000 2500
0 50 100 150 200
Days since the graft
L: 31
30 40 50 60 70 80
0 500 1000 1500
0 50 100 150 200 250
Days since the graft
M: 32
50 100 150
0 500 1000 1500 2000
0 50 100 150 200
Days since the graft
N: 34
40 60 80 100
0 500 1000 1500
0 50 100 150 200
Days since the graft
O: 36
50 60 70 80 90 100
0 500 1000 1500 2000
0 50 100 150 200 250
Days since the graft
CEMB (pg/mg of tissue) and CPBMC (pg/106 cells) Cblood (ng/mL)
Fig. S1: Longitudinal follow-up data of CsA-treated patients with more than 3 consecutive time points, with the patients numbers. X axis represent time from the transplantation (days); left Y axis represents CsA concentration as CEMB in pg/mg of tissue (squares) and CPBMC in pg/106 cells (rounds);
right Y axis represents Cblood in ng/ml (triangles). Vertical arrows indicate visits with a BPAR. A larger arrow shows the moderate rejection of patient 24. BPAR: biopsy-proven acute rejection; CEMB: endomyocardial biopsy calcineurin inhibitor concentration; Cblood: whole blood pre-dose calcineurin inhibitor concentration; CNI: calcineurin inhibitor; CPBMC: peripheral blood mononuclear cells calcineurin inhibitor concentration; CsA: cyclosporin A.
A: 01
0 200 400 600
0 50 100 150
0 5 10 15 20
Days since the graft
B: 03
200 300 400 500 600 700
0 20 40 60
0 5 10 15 20
Days since the graft
C: 04
300 400 500 600 700 800
0 20 40 60 80
0 2 4 6 8
Days since the graft
D: 05
600 700 800 900 1000 1100
0 50 100 150
5 6 7 8 9 10 11
Days since the graft
E: 06
400 600 800
0 10 20 30 40
6.5 7.0 7.5 8.0
Days since the graft
F: 10
300 400 500 600 700 800
0 50 100 150
3 4 5 6 7 8
Days since the graft
G: 12
600 800 1000 1200
0 5 10 15 20 25
5.5 6.0 6.5 7.0 7.5 8.0
Days since the graft
H: 13
500 600 700 800 900
0 10 20 30 40 50
5.0 5.5 6.0 6.5 7.0 7.5
Days since the graft
I: 15
600 800 1000
0 20 40 60
4 6 8 10 12
Days since the graft
J: 16
700 800 900 1000 1100 1200
0 50 100 150
4 5 6 7 8 9
Days since the graft
K: 20
200 300 400 500
20 25 30 35 40 45
6 7 8 9 10 11
Days since the graft
L: 21
300 400 500 600 700 800
0 20 40 60 80
5 6 7 8 9 10
Days since the graft
M: 22
200 300 400 500
0 20 40 60 80
6 7 8 9 10 11
Days since the graft
N: 24
250 300 350 400 450 500
0 10 20 30 40 50
5 6 7 8 9
Days since the graft
O: 28
100 200 300
0 20 40 60 80
8 10 12 14 16
Days since the graft
P: 31
50 100 150 200
0 50 100 150
0 5 10 15 20 25
Days since the graft
Q: 33
140 160 180 200 220 240
0 10 20 30 40 50
3 4 5 6 7
Days since the graft
R: 35
30 40 50 60
0 20 40 60 80
4 6 8 10 12
Days since the graft
CEMB (pg/mg of tissue) and CPBMC (pg/106 cells) Cblood (ng/mL)
Fig. S2: Longitudinal follow-up data of TAC-treated patients with more than 3 consecutive time points, with the patients numbers. X axis represent time from the transplantation (days); left Y axis represents TAC concentration as CEMB in pg/mg of tissue (squares) and CPBMC in pg/106 cells (rounds);
right Y axis represents Cblood in ng/ml (triangles). Vertical arrows indicate visits with a BPAR. BPAR:
biopsy-proven acute rejection; CEMB: endomyocardial biopsy calcineurin inhibitor concentration;
Cblood: whole blood pre-dose calcineurin inhibitor concentration; CNI: calcineurin inhibitor; CPBMC: peripheral blood mononuclear cells calcineurin inhibitor concentration; TAC: tacrolimus.