Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of nateglinide, cilostazol and its active metabolite 3,4-dehydro-cilostazol in Wistar rat plasma and its application to pharmacokinetic study

Varanasi, K.K.V.S.; Sridhar, Vinay; Potharaju, Suresh; Shraddha, R.; Sivakumar, Sasirekha; Sabapathi, S. Kanaga; Satheeshmanikandan, T.R.S.; Kumar, V.V.S. Swaroop

doi:10.1016/j.jchromb.2008.02.013

Cited by 18 publications

(12 citation statements)

References 19 publications

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“…The PK of cilostazol was explained well using a typical two-compartment model. The estimated PK parameters for cilostazol were similar to those reported previously [15]. Although data regarding the active metabolites of cilostazol (3,4-dihydrocilostazol and 4 0 -trans-hydroxy-cilostazol) were not available, according to previous reports, the major active metabolites of cilostazol are predicted to have PK patterns similar to that of the parent drug [16].…”

Section: Discussionsupporting

confidence: 80%

Semi‐Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents

Yun

Kang

Lee

et al. 2014

Basic Clin Pharma Tox

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Antiplatelet agents are a class of pharmaceuticals that decrease platelet aggregation and thus inhibit thrombus formation. We examined the relationships between plasma concentrations of antiplatelet agents (triflusal, clopidogrel and cilostazol) and the platelet aggregation inhibitory effect after dosing. We used triflusal, cilostazol and clopidogrel for the development of a semimechanistic PK/PD model. The drugs chosen are used widely and reflect various mechanisms of antiplatelet agents. Time courses of plasma concentrations of the antiplatelet agents and their platelet aggregation effects were analysed using ADPAT V. Pharmacokinetic profiles were fitted to an extended parent-metabolite pharmacokinetic model, based on a two-compartment model, and the pharmacodynamic effects of the agents were fitted to a platelet aggregation effect model that consisted of the following parameters: K s , the active-form platelet synthesis rate constant; K, the apparent reaction rate constant of the agent and active-form platelets; K el-PRP , the apparent rate constant of platelets; and e, an intrinsic activity parameter. This semi-mechanistic PK/PD model described well the relationship between plasma concentrations of antiplatelet agents and platelet aggregation effects. In addition, the estimated parameters were suitable for the explanation of the agents and also have a good correlation with platelet characteristics, such as platelet half-life and platelet aggregation baseline effects. Specifically, we discovered the strong correlations between estimated K parameter and in vitro drug activity. We conclude that this semi-mechanistic PK/PD model explained drug PK/PD characteristics well and will be useful for accurate predictions of antiplatelet effect in the clinical situations.

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Section: Discussionsupporting

confidence: 80%

Semi‐Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents

Yun

Kang

Lee

et al. 2014

Basic Clin Pharma Tox

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“…In addition, tolbutamide that is known to bind on the same site of SUR1 as nateglinide failed to induce GLP-1 release by this cell line. Furthermore, a major metabolite of nateglinide (M1), 35,36) which induced insulin release from rat pancreatic islets at the same concentration as nateglinide itself (Fig. 7), did not induce GLP-1 secretion by NCI-H716 cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

Nateglinide Stimulates Glucagon-Like Peptide-1 Release by Human Intestinal L Cells via a KATP Channel-Independent Mechanism

Kitahara

Miura

Yasuda

et al. 2011

Biological & Pharmaceutical Bulletin

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The incretin effect is markedly reduced in patients with type 2 diabetes, mainly due to defective glucagon-like peptide-1 (GLP-1) secretion from the intestinal L cells in response to stimulation by various nutrients. 1,2) This leads to impairment of early-phase insulin secretion after food intake and consequently results in postprandial hyperglycemia and hyperlipidemia. [3][4][5][6] GLP-1 is an incretin hormone that is released by intestinal L cells following their stimulation by nutrients, 7,8) and it promotes glucose-stimulated insulin secretion by pancreatic bcells. GLP-1 has also been reported to have various other beneficial effects, such as promoting b-cell proliferation, 9) suppressing glucagon release, 10) suppressing food intake, 11,12) slowing gastric emptying, 13,14) and cardiovascular protection.15) Therefore, restoration of GLP-1 secretion by intestinal L cells could be an important new therapeutic option for the management of metabolic syndrome. Although the exact mechanism of GLP-1 secretion by intestinal L cells remains to be elucidated, the sulfonylurea receptor 1 (SUR1)/K ATP channel, 16,17) Na ϩ /glucose co-transporter 1 (SGLT1), 18) glucose transporter 2 (GLUT2), 19) sweet taste receptor, 20)TGR5 21) and G-protein coupled receptors (GPRs) [22][23][24][25] have all been reported to be involved in this process. In the present study, we investigated the effect of nateglinide on GLP-1 secretion by human intestinal L cells.Nateglinide is a short-acting insulin secretagogue with a rapid effect, which restores early-phase insulin secretion in patients with type 2 diabetes by rapidly binding to SUR1 [26][27][28][29][30] and thus suppresses postprandial hyperglycemia. It has been unclear whether or not GLP-1 is involved in these effects of nateglinide. Recently, Duffy et al. reported that nateglinide increases the plasma GLP-1 level by inhibiting dipeptidyl peptidase IV (DPP IV), 31) but the influence of nateglinide on GLP-1 secretion is still unknown. Therefore, we investigated the effect of nateglinide on GLP-1 secretion in vivo by monitoring GLP-1 levels in the portal venous blood after oral administration of nateglinide to normal Wistar rats. We also conducted an in vitro study to assess the direct effect of nateglinide on GLP-1 secretion by human intestinal L cells (NCI-H716). MATERIALS AND METHODSAnimals Male Goto-Kakizaki (GK) rats and male Wistar rats (6 weeks old) were purchased from Japan SLC Inc. (Hamamatsu, Japan). The animals were housed in individual polycarbonate cages with woodchip bedding, and were provided with food and water ad libitum. The animal room was maintained on a 12-h light/dark cycle (7 a.m.-7 p.m.: dark; 7 p.m.-7 a.m.: light), with a temperature range of 22Ϯ1°C and a relative humidity of 55Ϯ5%, throughout the experimental period. These animal experiments were performed in accordance with the Guiding Principles for the care and use of laboratory animals approved by the Japanese Pharmacological Society. In addition, this study was approved by the Animal Care and Use Committ...

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“…In some cases matrix effects were not investigated [45][46][47][48][49]. Analysts should bear in mind that endogenous compounds can induce matrix effects without being present in the chromatogram.…”

Section: Literature Overviewmentioning

confidence: 99%

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

Eeckhaut

Lanckmans

Sarre

et al. 2009

Journal of Chromatography B

681

379

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Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of nateglinide, cilostazol and its active metabolite 3,4-dehydro-cilostazol in Wistar rat plasma and its application to pharmacokinetic study

Cited by 18 publications

References 19 publications

Semi‐Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents

Semi‐Mechanistic Modelling and Simulation of Inhibition of Platelet Aggregation by Antiplatelet Agents

Nateglinide Stimulates Glucagon-Like Peptide-1 Release by Human Intestinal L Cells via a KATP Channel-Independent Mechanism

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

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