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

Abstract

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.

Tadalafil Attenuates γ-Rays-Induced Hepatic Injury in Rats

“…33, No.1 (2020) the radiation episode. It is already known that PDE-5, including Tadalafil represents a potential approach against the evolution of diseases in which oxidative stress has a critical role, so Tadalafil is currently being used in the treatment of pulmonary hypertension (Shen et al, 2020).…”

“…Tadalafil induces cytoprotection and promotes cardio protection in mice (Koka et al, 2020). Recently, it is prescribed for treating pulmonary hypertension (Shen et al, 2020), and as a novel therapeutic method for the treatment of Alzheimer's disease, lower urinary tract signs as a consequence of nonmalignant prostate hyperplasia and in irritable Egypt. J. Rad.…”

A concise review of bioanalytical methods of small molecule immuno‐oncology drugs in cancer therapy

“…The fluorescence detector was operated under time‐programmed emission set at 330, 410 and 370 nm for tadalafil, dapoxetine and IS (avanafil), respectively; the excitation wavelength was set at 236 nm for both the analytes and IS (Hegazy, Kessiba, Abdelkawy, & Gindy, 2015). Shen, Chen, Wang, Huang, and Luo (2020) reported a HPLC method with DAD (diode array detection) for the quantification of tadalafil and carbamazepine (IS). The chromatographic separation was done on a Zorbax Eclipse XDB‐C 18 column maintained at 35°C with an isocratic elution consisting of acetonitrile:0.2% TFA:water (48:10:42, v/v/v) at a flow‐rate of 1.0 ml/min and the DAD detector was set at 286 nm.…”

“…The chromatographic separation was done on a Zorbax Eclipse XDB‐C 18 column maintained at 35°C with an isocratic elution consisting of acetonitrile:0.2% TFA:water (48:10:42, v/v/v) at a flow‐rate of 1.0 ml/min and the DAD detector was set at 286 nm. The extraction of tadalafil from rat plasma was performed by LLE using ethyl acetate (Shen, Chen, Wang, Huang, & Luo, 2020). Choi, Lee, Jang, Byeon, and Park (2017) developed a HPLC–UV method for the quantification of tadalafil in rat plasma.…”

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

“…Although there are some differences in the pharmacokinetics of different species, the results of animal experiments can provide some reference for clinical medication [32]. Therefore, clinically, when dexmedetomidine is combined with parecoxib, we should not only pay attention to the enhancement of the analgesic effect caused by the combination but also pay attention to the adverse drug reactions caused by drug-drug interactions.…”