Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Figures & data

Figure 1 Chemical structures of resveratrol (A) and saquinavir (B).

Figure 2 Effect of RESV on the intestinal CYP 3A mediated metabolism of SQV.

Notes: Data are presented as mean ± SD, n=3. Significant differences were determined by one-way ANOVA with Duncan’s multiple range test, **P<0.01 compared with the control group (no CYP 3A); ^##P<0.01 compared with the 0 μM RESV group.
Abbreviations: ANOVA, analysis of variance; CYP 3A, cytochrome P450 3A; RESV, resveratrol; SD, standard deviation; SQV, saquinavir; KET, ketoconazole.

Figure 3 Effect of RESV on the accumulation of SQV in MDCKII-MDR1 cells.

Notes: Data are presented as mean ± SD, n=4. Significant differences were determined by one-way ANOVA with Duncan’s multiple range test, *P<0.05; **P<0.01 compared with the control group.
Abbreviations: ANOVA, analysis of variance; MDCK, Madin–Darby canine kidney; RESV, resveratrol; SD, standard deviation; SQV, saquinavir; VER, verapamil.

Figure 4 Effect of RESV on the accumulation of SQV in MDCKII-MDR1 cells.

Notes: Data are presented as mean ± SD, n=4. Significant differences were determined by one-way ANOVA with Duncan’s multiple range test, **P<0.01 compared with the control group.
Abbreviations: ANOVA, analysis of variance; MDCK, Madin–darby canine kidney; RESV, resveratrol; SD, standard deviation; SQV, saquinavir; VER, verapamil.

Figure 5 Plasma concentration–time curves of SQV.

Notes: Mean plasma concentration–time curves of SQV after a single oral dose administration of SQV (30 mg/kg) with or without oral coadministration of RESV (20 mg/kg). Each point represents the mean ± SD, n=5.
Abbreviations: RESV, resveratrol; SD, standard deviation; SQV, saquinavir.

Table 1 Pharmacokinetic parameters of SQV after an oral dose of 30 mg/kg with or without oral coadministration of RESV 20 mg/kg

Parameter (unit)	SQV (30 mg/kg, oral)
	Control	RESV (20 mg/kg, oral)
AUC0–∞ (ng⋅h/mL)	258.06±126.79	177.92±90.52
Cmax (ng/mL)	59.42±35.23	64.66±24.37
Tmax (h)	4 (0)	0.25 (0)**
t1/2 (h)	6.34±1.73	5.77±0.56
MRT0–∞ (h)	6.73±1.95	5.60±1.11
CL/F (L/h/kg)	134.91±53.90	203.67±87.17
RBa (%)	100	68.95

Notes: Data are presented as mean ± SD except for T_max, for which the median (interquartile range) is reported. n=5 for each group.

** P<0.01 compared with control group.

a Relative bioavailability (RB%) = AUC_coadmin/AUC_control ×100.

Abbreviations: AUC, area under the curve; CL/F, clearance; h, hours; max, maximum; RESV, resveratrol; SD, standard deviation; SQV, saquinavir; t_1/2, terminal elimination half-life; MRT, mean residence time.