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Table 4 Physiological, experimental, and final calculated parameters for the diphenhydramine PBPK model established in this study

From: Pharmacokinetic modeling of over-the-counter drug diphenhydramine self-administered in overdoses in Japanese patients admitted to hospital

Parameter Value for diphenhydramine
Model input parameters
 Molecular weight 255
 Octanol–water partition coefficient 3.45
 Plasma unbound fraction 0.216
 Blood–plasma concentration ratio 0.898
 Liver–plasma concentration ratio 3.27
 Fraction absorbed × intestinal availability 0.436
 Absorption rate constant, 1/h 1.36 ± 0.01 a
 Transfer rate constant (k12), 1/h 0.107 ± 0.001 a
 Transfer rate constant (k21), 1/h 0.0437 ± 0.0001 a
 Volume of systemic circulation, L 117 ± 1
 Hepatic intrinsic clearance, L/h 100 ± 1
 Hepatic clearance, L/h 17.7
 Renal clearance, L/h 0.3
Estimated levels
 Cmax in plasma, ng/mL 0.209 (1.07) b
 AUC in plasma, ng h/mL 1.46 (1.07) b
 Cmax in liver, ng/mL 2.93
 AUC in liver ng h/mL 10.7
 Cmax in kidney, ng/mL 1.43
 AUC in kidney ng h/mL 9.96
Reported values [12, 13]
 Maximum drug concentration time, h [12] 2.5
 Cmax in plasma, ng/mL [12] 0.195
 AUC in plasma, ng h/mL [12] 1.36
 Half-life, h [12] 12
 Bioavailability [12] 0.34
 Urinary excretion of unchanged drug [13] 0.01 c
  1. The plasma unbound fraction, octanol–water partition coefficient, blood-to-plasma concentration ratio, and liver-to-plasma concentration ratio of diphenhydramine were estimated using in silico tools [14]
  2. aData are means ± standard deviations by fitting to measured concentrations
  3. bValues in parentheses of estimated levels are ratios to the reported values taken from the literature (shown in Fig. 1A, [12]) after 0.1 mg administrations
  4. c Urinary excretion ratio was taken from the literature [13] after 100 mg administrations