Table 3.

Comparison of the peak concentrations and AUC in blood and liver after oral and dermal exposure towards coumarin. C _max⁡ and AUC of coumarin were modelled in liver and in blood after 0.1 mg/kg by the oral route (extent of absorption 100%; half-life of absorption 20 min) and dermal route (extent of absorption 100%; half-life of absorption 30 min and 960 min dependent on the cosmetic preparation). It can be seen that the AUC in the liver is identical because the amount absorbed and reaching the liver is the same. However, because of differences in the absorption half-life C _max⁡ in the liver differs. In blood, AUC is different due to first pass in the liver. Even if the extent of absorption is identical the amount of coumarin reaching the systemic circulation after oral exposure is lower than after dermal exposure. C _max⁡ in blood depends on the rate of absorption, expressed as half-life. If half-life of dermal absorption is similar to the oral absorption (30 min versus 20 min), C _max⁡ is higher after dermal exposure (due to first pass in the liver after oral exposure and no first pass in the skin). If half-life of dermal absorption is prolonged as compared to the oral half-life of absorption (960 min versus 20 min). C _max⁡ is lower. Thus, it is not only the extent but also the rate of absorption, which matters in comparing oral and dermal exposure.

Dose (mg/kg)	Route of administration	Dose fraction which is absorbed	Absorption half-life (min)	C max⁡ liver (μg/kg)	AUC liver (μg/kg × h)	C max⁡ blood (μg/kg)	AUC blood (μg/kg × h)
0.1	Oral	1.0	20	3.6	1.8	3.1	32
0.1	Dermal	1.0	30	1.2	1.8	51	77
0.1	Dermal	1.0	960	0.06	1.8	2.7	77