TABLE 3.

Contribution of CYP1A2 to caffeine systemic clearance calculated from published mouse studies The difference between caffeine systemic clearance in the defined mouse strain and that in the Cyp1a KO mouse line was divided by the value of the systemic clearance in the defined mouse strain and then multiplied by 100% to obtain the contribution of CYP1A2. The clearance value measured in CYP1A2^−/− mice was used to calculate CYP1A2 contribution to caffeine systemic clearance in C57BL/6N mice reported by Buters et al. (1996).

Mouse Line	Dose	Route	Clearance	Reference	CYP1A2 Contribution
	mg/kg		ml/(h*kg)		%
CYP1A2−/−	2	i.p.	276	Buters et al., 1996	0
C57BL/6N	2	i.p.	2268	Buters et al., 1996	88
Cyp1a KO	5	PO	286	This study	0
C57BL/6J	5	PO	905	This study	68
hCYP1A1/1A2	5	PO	614	This study	53
C57BL/6J	5	PO	472a	Li et al., 2017	39
Swiss	20	PO	311b	Samojlik et al., 2016	8
Swiss	20	i.p.	398b	Samojlik et al., 2016	28
C57BL/6J	5	PO	726	Scheer et al., 2014	61
CD-COBS	1	i.v.	732	Walton et al., 2001	61
CD-1	20	i.p.	640	Kaplan et al., 1990	55
CD-1	40	i.p.	380	Kaplan et al., 1990	25

PO, per os (oral gavage).

^aAs it was not clear if the AUC reported in the paper was an AUCinf, caffeine clearance was calculated from the C57BL/6J mean pharmacokinetic profile presented in Fig. 2 in the publication (Li et al., 2017).

^bClearance was calculated by dividing dose by AUCinf.