In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer

Table 4 Pharmacokinetic parameters of CAP and its metabolites (5'-DFCR, 5'-DFUR and 5-FU) in HCT-116 cells after CAP administration (500 μM) (Mean ± SD, n = 4)

HCT-116		T_max (h)	C_max (ng/μg protein)	AUC_0-t (h*ng/μg protein)
Pre-metabolized by HepG2 cells for 0 h	CAP	24 ± 0	1.18 ± 0.55	47.15 ± 3.31
	5'-DFCR	48 ± 0	0.032 ± 0.007	0.92 ± 0.04
	5'-DFUR	48 ± 0	0.02 ± 0.001	0.31 ± 0.08
	5-FU	48 ± 0	0.001 ± 0.0005	0.01 ± 0.001
Pre-metabolized by HepG2 cells for 24 h	CAP	24 ± 0	1.28 ± 0.4	47.67 ± 2.21
	5'-DFCR	24 ± 0^**	0.05 ± 0.007^**	1.93 ± 0.33^**
	5'-DFUR	12 ± 0^**	0.09 ± 0.005^**	2.82 ± 0.17^**
	5-FU	48 ± 0	0.007 ± 0.0003^**	0.18 ± 0.03^**
Pre-metabolized by HepG2 cells for 48 h	CAP	12 ± 0^**	1.13 ± 0.02	38.63 ± 2.20^**
	5'-DFCR	24 ± 0^**	0.07 ± 0.004^**	2.52 ± 0.11^**
	5'-DFUR	12 ± 0^**	0.09 ± 0.003^**	3.26 ± 0.14^**
	5-FU	48 ± 0	0.01 ± 0.0005^**	0.33 ± 0.06^**

T_max time to peak concentration; C_max peak concentration; AUC_0-t area under the concentration–time curve from zero to the time of last measurable concentration
^*P < 0.05
^**P < 0.01 compared with the group of pre-metabolized by HepG2 cells for 0 h

ISSN: 1475-2867