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

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

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
C_max 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
C_max in plasma, ng/mL	4020	1450
AUC in plasma, ng h/mL	26,600	8680
Bioavailability	1	–
Urinary excretion of unchanged drug	0.03	–

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]
^aData are means ± standard deviations by fitting to measured concentrations
^bValues estimated by the simplified PBPK models for a normal single oral dose of 100 mg caffeine
^cValues in parentheses are ratios to the reported/observed values taken from the literature [3]
^dReported values for four Japanese male volunteers administered single oral doses of 100 mg caffeine [3]

ISSN: 2055-0294