The Effect of Grapefruit Juice on the Pharmacokinetics of Tadalafil in Rats

Abstract EN

We developed and validated a novel, sensitive, selective, and inexpensive high-performance liquid chromatography (HPLC) method for the determination of tadalafil in rats plasma and to investigate the effect of grapefruit juice on the pharmacokinetics of tadalafil in rats.

The ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) chromatography column can be used to separate tadalafil and carbamazepine (internal standard, IS).

A mixture of acetonitrile-0.2% trifluoroacetic acid-water (48 : 10 : 42, V/V/V) was used as the mobile phase with a flow rate of 1.0 mL/min.

The column temperature was set at 35.0°C.

The detection wavelength was set at 286 nm.

The tadalafil was extracted by ethyl acetate from plasma at the alkaline condition.

12 healthy male Sprague-Dawley (SD) rats were randomly divided into two groups, Group A (experimental group, received grapefruit juice 5 mL/kg for 7 days) and Group B (control group, received normal saline for 7 days).

All the rats were given a single dose of tadalafil (5 mg/kg) after the last administration.

The main pharmacokinetic parameters were calculated by DAS 2.0 software.

Under the conditions of this experiment, the plasma concentrations of tadalafil in the range of 10–2000 ng/ml had a good linear relationship.

The intra- and interday precision for tadalafil in plasma were less than 15%, and the relative recovery rate was good at low, medium, and high QC levels.

The Cmax of tadalafil in the control group and the experimental group was (725.89 ± 161.59) ng/mL and (1271.60 ± 179.31) ng/mL, t1/2 was (9.28 ± 2.07) h and (11.70 ± 1.47) h, AUC (0-t) was (7399.61 ± 696.85) ng·h/mL and (9586.52 ± 2048.81) ng·h/mL, and AUC(0-∞) was (7995.50 ± 707.23) ng·h/mL and (10639.43 ± 2235.94) ng·h/mL, respectively.

Results show that the Cmax of tadalafil in group A was 75.17% higher than that in group B, the Vz/F was also reduced, and the t1/2 was increased by 2.42 h.

The developed HPLC–DAD method for the determination of tadalafil in rats plasma was accurate, reproducible, specific, and it was found to be suitable for the pharmacokinetics of tadalafil and food-drug interactions.

Grapefruit juice can inhibit the metabolism of tadalafil and increase the exposure of tadalafil in rats.