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.
Highlights
Tadalafil is a competitive inhibitor of PDE-5, which prevents the degradation of cyclic guanosine monophosphate, leading to an increase in cGMP and induction of corpus cavernosum smooth muscle relaxation, thereby increasing blood flow and causing penile erection [1, 2]
Tadalafil has been approved for pulmonary arterial hypertension (PAH) [3], erectile dysfunction (ED) [4], benign prostatic hyperplasia (BHP) [5], the lower urinary tract symptoms (LUTS) [6], and so on
Representative chromatograms of a blank plasma sample, a plasma sample spiked with tadalafil and CBZ, and a rat sample obtained 1.5 h after oral administration of tadalafil were shown in Figure 1. e retention time of tadalafil and CBZ were 6.41 and 5.44 min, respectively
Summary
Tadalafil is a competitive inhibitor of PDE-5, which prevents the degradation of cyclic guanosine monophosphate (cGMP), leading to an increase in cGMP and induction of corpus cavernosum smooth muscle relaxation, thereby increasing blood flow and causing penile erection [1, 2]. Tadalafil has been approved for pulmonary arterial hypertension (PAH) [3], erectile dysfunction (ED) [4], benign prostatic hyperplasia (BHP) [5], the lower urinary tract symptoms (LUTS) [6], and so on. Tadalafil was approved for the treatment of ED in 2009. Tadalafil was rapidly absorbed after oral administration and reaches Cmax 2 hours after taking the drug. E absorption rate and degree of tadalafil are not affected by food, so this product can be taken with or without food. Tadalafil is metabolized in the body primarily to inactive catechol metabolites by CYP3A4. Tadalafil is mainly excreted by feces, and about 1/3 of the metabolized drugs are excreted from the urine [7,8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
