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Table 2 Physiological, experimental, and final calculated parameters for PBPK models of caffeine and paraxanthine established in this study

From: Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital

Parameter Caffeine Paraxanthine
Model input parameters
 Molecular weight 194 180
 Octanol–water partition coefficient −0.04 −0.279
 Plasma unbound fraction 0.758 0.798
 Blood–plasma concentration ratio 0.822 0.798
 Liver–plasma concentration ratio 0.681 0.689
 Fraction absorbed × intestinal availability 1
 Absorption rate constant, 1/h 4.94 ± 0.15 a
 Volume of systemic circulation, L 18.8 ± 0.1 a 74.5 ± 0.1 a
 Hepatic intrinsic clearance, L/h 2.70 ± 0.05 a 6.66 ± 0.08 a
 Hepatic clearance, L/h 2.00 5.04
 Renal clearance, L/h 0.06 0.15
Estimated values b
 Cmax in plasma, ng/mL 5340 (1.3) c 649 (0.45) c
 AUC in plasma, ng h/mL 29,300 (1.1) c 3440 (0.40) c
Reported levels d
 Cmax in plasma, ng/mL 4020 1450
 AUC in plasma, ng h/mL 26,600 8680
 Bioavailability 1
 Urinary excretion of unchanged drug 0.03
  1. The plasma unbound fraction, octanol–water partition coefficient, blood-to-plasma concentration ratio, and liver-to-plasma concentration ratio of caffeine and paraxanthine were estimated using in silico tools [23]
  2. aData are means ± standard deviations by fitting to measured concentrations
  3. bValues estimated by the simplified PBPK models for a normal single oral dose of 100 mg caffeine
  4. cValues in parentheses are ratios to the reported/observed values taken from the literature [3]
  5. dReported values for four Japanese male volunteers administered single oral doses of 100 mg caffeine [3]