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Table 4 Population parameter estimates and relative standard errors (%) of ( R )-[ 11 C]verapamil brain model are shown for all investigated brain regions

From: Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood–brain barriers studied with (R)-[11C]verapamil positron emission tomography

  Species
  Rat Human
Brain region WB *,a WB b CS EC SHipp THipp Th Cer FMC WB *,a WB b
OFV −604 −1676 −1420 −1652 −1500 −954 −1559 −1562 −1365 7799 −357
Model parameters            
V br1 (ml) 0.132 0.132 0.119 0.155 0.151 0.129 0.156 0.192 0.088 2.29 3.17
(10.5) (11.3) (10) (11.4) (9.74) (27.2) (12.2) (19.2) (15.8) (−) (−)
V br2 (ml) 2 2 2 2 2 2 2 2 2 13.0 18.4
(−) (−) (−) (−) (−) (−) (−) (−) (−) (−) (−)
Q in (ml·min−1) 5.48 5.62 2.05 3.32 2.49 1.98 2.43 2.44 1.79 713 588
(13.0) (12.5) (12.8) (16.8) (12.7) (24.5) (11.3) (14.2) (19.2) (−) (−)
Q out (ml·min−1) 3.56 3.60 3.45 3.91 4.56 2.99 4.39 3.01 1.97 1410 1080
(12.6) (12.5) (12.5) (16.3) (12.5) (21.8) (11.3) (13.9) (19.1) (−) (−)
Q br (ml·min−1) 0.115 0.115 0.114 0.111 0.113 0.108 0.129 0.118 0.12 1.26 1.71
(3.2) (3.05) (3.43) (3.71) (3.87) (4.63) (3.45) (3.24) (3.58) (−) (−)
Residual error brain 0.404 0.382 0.44 0.387 0.421 0.571 0.016 0.407 0.454 0.295 0.27
(5.1) (4.61) (5.3) (6.25) (4.18) (14.4) (3.93) (5.72) (6.32) (−) (−)
Covariates            
Effect of pilocarpine induced SE            
EffSE c 1.84 1.84 1.88 1.73 1.86 2.21 1.77 0.924 2.3 (−) (−)
(10.4) (11.7) (13.8) (13.5) (13.2) (24.7) (12.9) (20.5) (15.8)   
Effect of tariquidar            
Efftariquidar (3 mg/kg or 2 mg/kg)d 0.219 0.161 0.114 0.233 0.119 0.15 0.12 0.226 0.194 0.993 0.483
(5.84) (4.16) (3.89) (5.54) (5.49) (5.51) (5.33) (5.31) (4.42) (−) (−)
Efftariquidar (15 mg/kg)d 0.168 0.135 0.101 0.215 0.101 0.134 0.103 0.148 0.155 (−) (−)
(5.22) (6.94) (7.71) (6.56) (9.3) (7.61) (9.01) (8.65) (7.74) - -
Effect of scan on tariquidar induced P-gp inhibition            
Effscan d (−) 1.33 1.29 1.37 1.29 1.25 1.21 1.52 1.4 (−) 2.28
- (5.67) (6.78) (5.47) (7.1) (6.21) (6.08) (6.97) (6.06) - (−)
  1. All (R)-[11C]verapamil plasma model parameter estimates outlined in Figure 2, obtained from final plasma model were fixed and the parameter estimate for the second brain compartment V br2 was fixed in rats to 2 ml. Parameters are given for the whole brain excluding (WB*) and including (WB) the increase of (R)-[11C]verapamil brain uptake during and after treatment with tariquidar, corpus striatum (CS), entorhinal cortex (EC), septal hippocampus (SHipp), temporal hippocampus (THipp), thalamus (TH), cerebellum (Cer), and frontal motor cortex (FMC) for rat; WB* and WB for human. aWB* is the whole brain region excluding data from 60 to 140 min rat or 40 to 120 min human (baseline and post-inhibition scan are considered, as used for kinetic modeling). bWB is the whole brain region including data from 60 to 140 min rat or 40 to 120 min human (baseline, during, and after tariquidar, and post-inhibition scan are considered). cEffSE was a significant covariate on V br1. dThe effect of tariquidar, Efftariquidar, is on Q out the efflux clearance from the central brain compartment to the plasma compartment, while Effscan also takes into account changes occurring between scans (baseline or post-inhibition).