Article Figures & Data
Figures
- Fig. 1.
Structure of FA.
- Fig. 2.
Reversible (A) and time-dependent (B) inhibition of CYP3A4-catalyzed midazolam-1′-hydroxylase activity in human liver microsomes by FA. (A) Competitive inhibition plot of percent activity remaining (1′-hydroxymidazolam formation) versus log of FA concentration. Values are plotted as the mean (n = 4) and error bars indicate the S.D. Curve fitting was used to determine IC50. (B) TDI, natural log (LN) of percent activity remaining (1′-hydroxymidazolam formation) versus FA concentration. Concentrations are shown in the legend. Linear regression was used to calculate the negative slope (kobs) at each FA concentration. The inset shows TDI kobs plotted versus FA concentrations and a three-parameter nonlinear regression was performed to calculated KI and kinact. The solid line illustrates the line of best fit and the dotted lines represent the 95% confidence band.
- Fig. 3.
Concentration-dependent inhibition of human OATP1B1 and OATP1B3 (A) and rat Oatp1a4 and Oatp1b2 (B) uptake transporters by FA. Transporter inhibition was investigated by determining the uptake of rosuvastatin (5 μM) in the HEK cell line overexpressing the respective transporters. Data are expressed as the mean of three replicates and error bars represent the S.D.
- Fig. 4.
Concentration-dependent inhibition of human MDR1 by FA. Inhibition of MDR1 activity was investigated by determining the digoxin efflux across MDR1-MDCKII monolayers. Data are expressed as the mean of three replicates. The solid line illustrates the line of best fit and the dotted lines represent the 95% confidence band.
- Fig. 5.
Mean plasma concentration-time profile of rosuvastatin in male Wistar-Han rats after a single oral dose of rosuvastatin (3 mg/kg) and after a single oral dose of rosuvastatin (3 mg/kg) dosed 0.25 hours after oral FA (250 mg/kg). Data are expressed as means ± S.D. (n = 3 animals). Control rosuvastatin animals are represented with circles and FA with filled triangles. The inset shows the mean plasma concentration-time profile of FA in male Wistar-Han rats (n = 3) after a single oral dose of 250 mg/kg.
Tables
- TABLE 1
Pharmacokinetic parameters of rosuvastatin after a single oral dose of 3 mg/kg to male Wistar-Han rats in the presence of vehicle or a single oral dose of FA (250 mg/kg)
Rosuvastatin was administered 0.25 hours after pretreatment with FA. Data are presented as means ± S.D. from three male rats and were derived from noncompartmental analysis.
Treatment Cmax Tmax t1/2 AUC(0–tlast) ng/ml h h ng⋅h/ml Vehicle 7.63 ± 3.99 1.08 ± 1.01 2.29 ± 1.63 15.0 ± 5.80 FA (250 mg/kg) 147 ± 54.5a 2.92 ± 1.15 3.52 ± 4.25 369 ± 90.0a ↵a t test with Welch's correction of unpaired t test data (variances/S.D. were not equal between groups, P < 0.05).
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