Naringenin alters the pharmacokinetics of ranolazine in part through the inhibition of cytochrome P450 (3A4) and P-glycoprotein

Future Journal of Pharmaceutical Sciences

Table 1 Naringenin's impact on ranolazine's pharmacokinetics in SDS and MDS (n = 6)

Pharmacokinetic parameter	Ranolazine	Ranolazine + Naringenin (STD)	Ranolazine + Naringenin (MTD)
Cmax (ng/mL)	231 ± 10.16	303.67 ± 9.46*	325.67 ± 21.81*
Tmax (h)	4.5 ± 0.32	4.5 ± 0	4.5 ± 0
AUC_0–18(ng/mL/h)	1293.54 ± 37.18	1505.38 ± 100.30**	1575.42 ± 76.98**
AUC_0–∞ (ng/mL/h)	1328.52 ± 39.69	1546.74 ± 104.05	1616.01 ± 78.82
AUC_{% extrapolation}	2.6 ± 0.34	2.67 ± 0.44	2.51 ± 0.33
AUMC_0–18 (ng/mL/h2)	8677.67 ± 305.37	9739.13 ± 906.61**	10,265.99 ± 646.85**
AUMC_0–∞ (ng/mL/h2)	9307.95 ± 344.15	10,493.22 ± 964.19	9236.7 ± 4566.05
MRT_0–18 (h)	6.71 ± 0.08	6.46 ± 0.21*	6.45 ± 0.17*
MRT_0–∞ (h)	7.01 ± 0.09	6.78 ± 0.2	6.74 ± 0.17
K_el(h⁻¹)	0.23 ± 0.01	0.23 ± 0.01*	0.23 ± 0.01*
t_1/2 (h)	3.02 ± 0.12	3.01 ± 0.11*	2.95 ± 0.1*

AUC Area under the curve, AUMC Area under the moment curve, t_1/2 half-life; Cmax Maximum concentration, Tmax Time required to reach maximum concentration, MRT Mean retention time
*p < 0.05, when compared to ranolazine treatment alone
**p < 0.01, when compared to ranolazine treatment alone