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Table 1 Parameter estimates of final population pharmacokinetic model

From: Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics

  Bootstrap analysis Median [5-95th percentiles]
Parameters Estimates (RSE%) BAV (RSE%) Estimates BAV
Clozapine     
CLclo/F (L/min) 0.5(20.3)   0.463[0.358-0.661]  
Vclo-p/F (L) 19.4(40.3)   18.9[5.43-31.59]  
Kaclo (1/min) 0.00801(14.7)   0.00815[0.0051-0.0095]  
Qclo/F (L/min) 2.01(40.8) 0.193(33.6) 2.08[0.58-3.43] 0.2[0.07-0.29]
Vclo-b/F (L) 0.214 FIXED    
Ktr1 (1/min) 0.0125(9.4) 0.05 (48.9) 0.0129[0.011-0.015] 0.047[0.0033-0.069]
Fclo 1 FIXED 0.259(37.1)   0.243[0.062-0.35]
Norclozapine     
Clclo-met/F (L/min) 0.055(24.8)   0.0584[0.04-0.0855]  
CLmet/F (L/min) 0.419(18.8) 0.111(74.8) 0.43[0.33-0.61] 0.08[0.0038-0.18]
Vmet-p/F (L) 2.95(38.6) 0.168(51.1) 3.02[1.91-5.55] 0.149[0.000047-0.27]
Kamet (1/min) 0.00277(31) 0.371(44.2) 0.00296[0.0015-0.0047] 0.319[0.065-0.54]
Qmet/F (L/min) 0.388(45)   0.386[0.229-0.768]  
Vmet-b/F (L) 0.25 FIXED    
Ktr2 (1/min) 0.00517(12.3)   0.00521[0.0045-0.0064]  
Fmet 1 FIXED    
Residual error (proportional)     
Parent-plasma 0.109(70)   0.084[0.029-0.19]  
Parent-brain 0.0367(27)   0.0371[0.023-0.055]  
Metabolite-plasma 0.0762(24.1)   0.0714[0.051-0.11]  
Metabolite-brain 0.014(18)   0.0133[0.0095-0.017]  
  1. Clo (Clozapine): CLclo/F (L/min) = apparent clearance of clozapine; Vclo-p/F (L) = apparent volume of distribution of clozapine in plasma; Kaclo (1/min) = absorption rate of clozapine; Qclo/F (L/min) = apparent intercompartmental clearance of clozapine;
  2. Vclo-b/F (L) = apparent volume of distribution of clozapine in brain; Ktr1 (1/min) = transit rate constant of clozapine.
  3. Met (Norclozapine): CLclo-met/F (L/min) = apparent clearance of clozapine to norclozapine; CLmet/F (L/min) = apparent clearance of norclozapine; Vmet-p/F (L) = apparent volume of distribution of norclozapine in plasma; Kamet (1/min) = absorption rate of norclozapine; Qmet/F (L/min) = apparent intercompartmental clearance of norclozapine; Vmet-b/F (L) = apparent volume of distribution of norclozapine in brain; Ktr2 (1/min) = transit rate constant of norclozapine.
  4. BAV = between animal variability.
  5. RSE% = percent relative standard error.