Evaluation of pharmacokinetic and pharmacodynamic parameters following single dose of sitagliptin in healthy Indian males

Sangle, Ganesh V.; Patil, Mohan; Deshmukh, Nitin; Shengule, Sushant; Kamble, Shantibhushan; Vuppalavanchu, Kiran Kumar; Kale, Sushil; Baig, Mirza Layeeq Ahmed; Singh, Geetchandra; Shaikh, J.; Tripathi, Jitendra Kumar; Aravindababu, P.

doi:10.1007/s00228-018-2433-5

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…Plasma DPP‐IV activity was measured using the method reported by Sangle et al 64 Briefly, 10 μL of 100 M Gly‐Pro‐7 amido‐4‐methylcoumarin hydrobromide as a substrate was added to 90 μL of plasma in a white polystyrene 96‐well half‐area plate (Product # 3688, Corning, USA). Fluorescence reading was recorded kinetically in a microplate reader (H1 Synergy, BioTek, USA) for 5 min at 60‐s time intervals (excitation at 360 nm and emission wavelength at 460 nm).…”

Section: Methodsmentioning

confidence: 99%

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Deshmukh,

Kalshetti,

Patil

et al. 2024

Clin Exp Pharma Physio

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Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon‐like peptide‐1 (GLP‐1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat‐regulating peptides such as GLP‐1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP‐1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP‐IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton‐induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co‐administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β‐hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high‐fat diet (HFD)‐fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP‐1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.

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Section: Methodsmentioning

confidence: 99%

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Deshmukh,

Kalshetti,

Patil

et al. 2024

Clin Exp Pharma Physio

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“…However, these differences didn't translate into meaningful clinical differences with regard to DPP-IV inhibition between the two population groups. 56,57,59 Interestingly, although the sitagliptin AUC increases proportionately with the dose, this is not true for the C max. Instead, the increase in this parameter is higher than proportional to an increase in the dose.…”

Section: Absorption and Bioavailabilitymentioning

confidence: 99%

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate

Charoo¹,

Abdallah

Bakheit

et al. 2022

Journal of Pharmaceutical Sciences

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“…PD profiles of both the treatment cohorts were determined by estimating plasma DPP-4 inhibition activity in a previously established assay method [17][18][19]. This fluorescence-based enzymatic assay utilised Gly-Pro-7 amido-4-methylcoumarin hydrobromide (Sigma- Aldrich, MO, USA) as a substrate.…”

Section: Pharmacodynamic Evaluationsmentioning

confidence: 99%

Comparative Clinical Pharmacokinetics and Pharmacodynamics of Investigational Once-Daily Sustained-Release (SR) Vildagliptin 100 mg Tablet Formulation with Conventional 50 mg Twice-Daily Regimen in Healthy Indian Males

Pote¹

2021

ijcsrr

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Background- Among the gliptins, vildagliptin is the only therapy requiring twice-daily dosing and thus adversely impacts patient adherence. To reduce dosing frequency, we developed a once-daily sustained-release (SR) vildagliptin 100 mg tablet formulation with potential to furnish comparable dipeptidyl peptidase-4 (DPP-4) inhibition coverage to the conventional twice-daily regimen. Objective- The current study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational once-daily SR vildagliptin 100 mg tablet formulation with the twice-daily dosage of marketed product, Galvus® in healthy Indian adult males after single and multiple-dose administration. Methods- Single and multiple-dose PK-PD assessment was conducted in separate clinical studies enrolling thirty-six healthy subjects under fed-condition. Each study was a randomized, open-label, two treatment, two-period, crossover design. Drug plasma concentrations were quantified by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. DPP-4 inhibition was estimated in the fluorescence-based assay. PK parameters were calculated from the plasma concentration-time curve employing Phoenix® WinNonlin® software. Formulation safety was evaluated by monitoring adverse events. Results- SR vildagliptin 100 mg tablet resulted in peak-less, nearly steady drug concentration-time profile. Thus, its mean PK characteristics after single [Cmax (147.7), AUC(0-24) (1645.04), Tmax (5.29 hr), t1/2 (4.61 hr)] and multiple-dose [Cmaxss (163.59), AUCss (0-24) (1815.36), and Tmaxss (4.65 hrs), t1/2ss (3.71 hr)] administrations were significantly distinct from the Galvus® twice-daily regimen. SR vildagliptin 100 mg tablet demonstrated more than 80% DPP-4 inhibition profile for approximately 23 hrs in both the studies which was comparable to Galvus® twice-daily regimen. Conclusions- Investigational SR vildagliptin 100 mg tablet formulation was found to be safe and well-tolerated. Its ability to provide nearly 80% DPP-4 inhibition coverage over 23 hrs post-dose may reduce the additional pill burden in patients on conventional twice-daily regimen.

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Evaluation of pharmacokinetic and pharmacodynamic parameters following single dose of sitagliptin in healthy Indian males

Abstract: Although, there are differences in pharmacokinetic parameters, no clinically meaningful differences were observed with respect to DPP-IV inhibition between Indian and non-Indian population.

Cited by 10 publications

References 32 publications

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate

Comparative Clinical Pharmacokinetics and Pharmacodynamics of Investigational Once-Daily Sustained-Release (SR) Vildagliptin 100 mg Tablet Formulation with Conventional 50 mg Twice-Daily Regimen in Healthy Indian Males

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