Pharmacokinetics and Bioequivalence of Two Empagliflozin, with Evaluation in Healthy Jordanian Subjects under Fasting and Fed Conditions

Hailat, Mohammad; Zakaraya, Zainab; Al-Ani, Israa; Meanazel, Osaid Al; Al-Shdefat, Ramadan; Anwer, Md. Khalid; Saadh, Mohamed J.; Dayyih, Wael Abu

doi:10.3390/ph15020193

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…Pharmacokinetic and pharmacodynamic properties of SGLT2 inhibitors. Compiled from[26,27,[31][32][33][34][35][36][37].…”

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confidence: 99%

SGLT2 Inhibitors as Potential Anticancer Agents

Basak,

Gamez,

Deb

2023

Biomedicines

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Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased glucose uptake in both mice and humans. Inhibition of its expression can robustly thwart tumor development in vitro and in vivo. SGLT2 inhibitors are a comparatively new class of antidiabetic drugs that have demonstrated anticancer effects in several malignancies, including breast, liver, pancreatic, thyroid, prostate, and lung cancers. This review aims to assess the extent of SGLT involvement in different cancer cell lines and discuss the pharmacology, mechanisms of action, and potential applications of SGLT2 inhibitors to reduce tumorigenesis and its progression. Although these agents display a common mechanism of action, they exhibit distinct affinity towards the SGLT type 2 transporter compared to the SGLT type 1 transporter and varying extents of bioavailability and half-lives. While suppression of glucose uptake has been attributed to their primary mode of antidiabetic action, SGLT2 inhibitors have demonstrated several mechanistic ways to combat cancer, including mitochondrial membrane instability, suppression of β-catenin, and PI3K-Akt pathways, increase in cell cycle arrest and apoptosis, and downregulation of oxidative phosphorylation. Growing evidence and ongoing clinical trials suggest a potential benefit of combination therapy using an SGLT2 inhibitor with the standard chemotherapeutic regimen. Nevertheless, further experimental and clinical evidence is required to characterize the expression and role of SGLTs in different cancer types, the activity of different SGLT subtypes, and their role in tumor development and progression.

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“…Pharmacokinetic and pharmacodynamic properties of SGLT2 inhibitors. Compiled from[26,27,[31][32][33][34][35][36][37].…”

mentioning

confidence: 99%

SGLT2 Inhibitors as Potential Anticancer Agents

Basak,

Gamez,

Deb

2023

Biomedicines

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“…A one-compartment model with first-order absorption and elimination adequately represented LEV pharmacokinetics 18 . Administering a combination of drugs and or food may alter their pharmacokinetics 19 , 20 . This study investigated the combination of date fruit molasses on LEV Pharmacokinetics in healthy rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of date molasses on levetiracetam pharmacokinetics in healthy rats

Dayyih

Layth

Hailat

et al. 2023

Sci Rep

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Twelve healthy eight-week-old male Wistar rats weighing 200 g were used. Rats were chosen randomly, and their tails were identified and separated into cages/groups. The first group received an oral dose of 11.5 mg of levetiracetam in 5 mL of water, and the second group was given date syrup (250 g mixed with 250 mL water) for seven days, then 11.5 mg LEV in 5 mL water on day 7. One week of preadministered date molasses significantly decreased levetiracetam pharmacokinetic parameters in rats, such as Cmax (72 vs. 14 ng/mL, p = 0.01), Tmax (1.78 vs. 0.44 h, p < 0.001), and AUC (880 vs. 258 ng.h/mL, p < 0.001). This decrease in plasma levetiracetam levels caused by date molasses could be attributed to decreased levetiracetam absorption. On the other hand, the current study discovered that rats given date molasses for a week had a reduced rate and extent of absorption. As a result, date molasses might increase the risk of epileptic seizures in oral LEV-treated ones.

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“…Empagliflozin was the first antidiabetic drug to minimize cardiovascular and overall mortality in T2DM patients [ 5 ] with elevated cardiovascular risk, confirmed by new and significant clinical trials with SGLT2i in preventing hyperglycemia-induced risks [ 6 ]. No therapy has demonstrated comparable reductions in cardiovascular and overall mortality in T2DM patients with proven cardiovascular risk to date in either a dipeptidyl peptidase-4 (DPP-4) inhibitor or a glucagon-like peptide-1 (GLP-1) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Validation and Determination of Empagliflozin Concentration in the Presence of Grapefruit Juice Using HPLC for Pharmacokinetic Applications

Abu Dayyih,

Zakaraya,

Hailat

et al. 2024

Molecules

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Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice’s impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid.

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Pharmacokinetics and Bioequivalence of Two Empagliflozin, with Evaluation in Healthy Jordanian Subjects under Fasting and Fed Conditions

Cited by 6 publications

References 24 publications

SGLT2 Inhibitors as Potential Anticancer Agents

SGLT2 Inhibitors as Potential Anticancer Agents

Effect of date molasses on levetiracetam pharmacokinetics in healthy rats

The Validation and Determination of Empagliflozin Concentration in the Presence of Grapefruit Juice Using HPLC for Pharmacokinetic Applications

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