TABLE 2

The effect of rifampicin on 1′-hydroxymidazolam (CYP3A4) and hydroxybupropion (CYP2B6) pharmacokinetics in HepaRG cells cultured in the bioreactor

The 1′-hydroxymidazolam and hydroxybupropion pharmacokinetics in cells treated with rifampicin (P450 activity 5 in Fig. 2) are compared with the pharmacokinetics directly before (P450 activity 4 in Fig. 2) introducing rifampicin into the system. The results are obtained from three different bioreactors. Published results on the effect of rifampicin in vivo on midazolam and hydroxybupropion pharmacokinetics are also shown.

	Before Rifampicin Treatment	After Rifampicin Treatment	Fold Change
CYP3A4
HepaRG bioreactor^{^a}
Formation rate_{1′-hydroxymidazolam} (nmol/h)	0.93 ± 0.25	4.4 ± 2.2^*	5.5 ± 4.0
In vivo^{^b}
CL_midazolam (l/h · 70 kg)	33 ± 10	62 ± 36	1.9
CYP2B6
HepaRG bioreactor^{^a}
Formation rate_{Hydroxybupropion} (nmol/h)	0.062 ± 0.017	0.38 ± 0.085^**	6.3 ± 1.5
In vivo^{^c}
Formation CL_{Hydroxybupropion} (ml/min)	62 ± 47	249 ± 189	3.8

↵* p ≤ 0.05;
↵** p < 0.01.
↵a Data are mean ± S.D.; n = 3.
↵b Data are from Yu et al. (2004).
↵c Data are from Kharasch et al. (2008).