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Table 5 Comparison of volumes of distribution ( V T ) values of naïve, 48-h SE rats, and humans obtained with Logan analysis, PK modeling, and nonlinear mixed effects modeling, respectively

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

Sample Logan analysis a PK modeling a(2T4K) Nonlinear mixed effects modeling
WB* Cer WB* Cer WB* WB Cer
Control rats        
Baseline 1.6 (16) 2.0 (19) 1.8 (16) 2.2 (18) 1.5 (18) 1.6 (18) 0.81 (20)
Post-inhibition 7.6 (13) 6.1 (9) 7.8 (14) 6.1 (9) 7.0 (19) 9.6 (18) 2.4 (21)
Increase after 3 mg/kg tariquidarb 4.8-fold 3.1-fold 4.4-fold 2.8-fold 4.6-fold 6.2-fold 4.4-fold
48-h post SE rats        
Baseline 1.4 (8) 1.3 (7) 1.5 (12) 1.5 (6) 1.5 1.6 0.81
Post-inhibition 7.4 (11) 3.5 (13) 7.6 (12) 3.6 (14) 7.0 9.6 2.4
Increase after 3 mg/kg tariquidarb 5.5-fold 2.6-fold 5.1-fold 2.4-fold 4.6-fold 6.2-fold 4.4-fold
Human        
Baseline scan 0.64 (1)   0.65 (6) - 0.54 (−) 0.51 (−) -
Post-inhibition 0.79 (1)   0.80 (2) - 0.49 (−) 0.79 (−) -
Increase after 2 mg/kg tariquidarb 1.2-fold   1.2-fold - No difference 1.5-fold -
  1. V T values were expressed as average and relative standard errors (%) for the WB region and Cer at baseline and post-inhibition scan. aLogan and 2T4K results were obtained from Bankstahl et al. [9] for rats and from Wagner et al. [30] for humans. bIncrease after tariquidar administration for NLME modeling is based on the estimated covariate effect Efftariquidar(1/Efftariquidar).