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

Table 2 Physiological, experimental, and final calculated parameters for loxoprofen PBPK model established in this study

Parameter	Loxoprofen	Reduced trans-alcohol metabolite of loxoprofen
Model input parameters
Molecular weight	246	248
Octanol–water partition coefficient	1.97	2.23
Plasma unbound fraction	0.0681	0.0559
Blood–plasma concentration ratio	0.799	0.782
Liver–plasma concentration ratio	1.15	1.49
Fraction absorbed × intestinal availability	1	–
Absorption rate constant, 1/h	6.17 ± 0.27 ^a	–
Volume of systemic circulation, L	4.67 ± 0.17 ^a	11.4 ± 0.3 ^a
Hepatic intrinsic clearance, L/h	76.3 ± 0.3 ^a	215 ± 1 ^a
Hepatic clearance, L/h	4.93	10.7
Renal clearance, L/h	0.10	1.1
Estimated values ^c
C_max in plasma, ng/mL	6940 (0.97) ^b	770 (0.86) ^b
AUC in plasma, ng h/mL	11,400 (1.1)^b	2380 (0.90) ^b
Reported levels
C_max in plasma, ng/mL ^d	7160	896
AUC in plasma, ng h/mL ^d	10,700	2650
Bioavailability ^d	1	–
Urinary excretion of unchanged drug ^d	0.02	–

The plasma unbound fraction, octanol–water partition coefficient, blood-to-plasma concentration ratio, and liver-to-plasma concentration ratio of loxoprofen and the reduced trans-alcohol metabolite of loxoprofen were estimated using in silico tools [15]
^a Data are means ± standard deviations by fitting to observed concentrations
^b Values in parentheses are ratios to the reported/observed values
^c PBPK modeled values for a virtual administration of 60 mg loxoprofen
^d Taken from the literature [4, 14], as shown in Fig. 1A

ISSN: 2055-0294