Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new glipizide research articles will be listed here shortly after becoming available to us.
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Medical research on glipizide
Acta Pharmacol Sin. 2008 Jul; 29(7): 789-99
Li L, Ma KT, Zhao L, Si JQ, Zhang ZS, Zhu H, Li J
Aim: The influence of niflumic acid (NFA), a Cl(-)channel antagonist, on the membrane potentials in smooth muscle cells (SMC) of the cochlear spiral modiolar artery (SMA) in guinea pigs was examined. Methods: The intracellular recording and whole-cell recording technique were used to record the NFA-induced response on the acutely-isolated SMA preparation. Results: The SMC had 2 stable but mutually convertible levels of resting potentials (RP), that is, one was near -45 mV and the other was approximately -75 mV, termed as low and high RP, respectively. The bath application of NFA could cause a hyperpolarization in all the low RP cells, but had little effect on high RP cells. The induced responses were concentration-dependent. Large concentrations of NFA (>/=100 micromol/L) often induced a shift of a low RP to high RP in cells with an initial RP at low level, and NFA (up to 100 micromol/L) had little effect on the membrane potentials of the high RP cells. However, when the high RP cells were depolarized to a level beyond -45 mV by barium and ouabain, NFA hyperpolarized these cells with the similar effect on those cells initially being the low RP. The NFA-induced response was almost completely blocked by charybdotoxin, iberiotoxin, tetraethylammonium, 1,2-bis(2- aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester, but not by 4-aminopyridine, barium, glipizide, apamin, ouabain, and CdCl2. Conclusion: NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1; 870(1): 135-139
Niu Z, Chen F, Sun J, Liu X, Wang Y, Chen D, He Z
A rapid, sensitive and specific high performance liquid chromatography-electrospray ionization tandem quadrupole mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of 3-n-butylphthalide in rat plasma. Following protein precipitation with acetonitrile, 3-n-butylphthalide and glipizide (internal standard, I.S.) were separated using a gradient elution program on a C(18) column and detected by mass spectrometry in positive ion mode with the multiple reaction monitoring (MRM) mode using the respective precursor to product ion combinations of m/z 191/145 for 3-n-butylphthalide and m/z 446/321 for glipizide, respectively. The total chromatographic running time was 2.5min. The method was linear over the concentration range of 11.14-3480.00ng/mL, using as little as 100muL plasma. The lower limit of quantification (LLOQ) was 5.57ng/mL. Finally, the method was successfully used to support a preclinical pharmacokinetic study of 3-n-butylphthalide in rats following intravenous administration.
Guang Pu Xue Yu Guang Pu Fen Xi. 2008 Mar; 28(3): 711-4
Zhang YM, Li X, Sun CS, Chen CF
The interaction of glipizide and hydroxypropyl-pcyclodextrin was investigated in the present paper. The stability constant and molar ratio of glipizide and hydroxypropyl-beta-cyclodextrin was calculated from the phase soluility diagram. The solid state inclusion complex of hydroxypropyl-beta-cyclodextrin/glipizide prepared by neutralization method was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). It was found that the phase solubility diagram of the HP-beta-CD solution showed a typical AL-type, suggesting the formation of a soluble complex of 1 : 1 molar ratio, and the stability constant was 359 L x mol(-1) at 25 degrees C. The spectra of IR, thermograph of DSC and XRD pattern of the inclusion complex were remarkably different from the glipizide and hydroxypropyl-beta-cyclodextrin/glipizide physical mixture, and indicated that hydroxypropyl-beta-cyclodextrin/glipizide inclusion complex displayed amorphous characteristic. The experiment of solubility of inclusion complex indicated that the solubility of inclusion complex increased 25-fold.
Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency.
Diabetes Obes Metab. 2008 Jul; 10(7): 545-55
Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein PP, Kaufman KD, Amatruda JM, Williams-Herman D
OBJECTIVE: To assess the safety of sitagliptin in patients with type 2 diabetes and moderate [creatinine clearance (CrCl) > or =30 to
New treatments for type 2 diabetes mellitus: combined therapy with sitagliptin.
Expert Opin Pharmacother. 2008 Jun; 9(9): 1495-507
Gagliardino JJ, Santoro S, Arellano S, Di Girolamo G
BACKGROUND: Sitagliptin is a highly selective oral dipeptidyl peptidase-4 inhibitor. This drug increases the plasma concentration of active glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide. These two hormones then simulate the secretion of insulin in a glucose-dependent manner and inhibit glucagon secretion, thus reducing circulating glucose levels. In animal models, GLP-1 increases beta-cell mass. OBJECTIVE: To review the efficacy and safety of sitagliptin in combined therapies (as add on or initial combination treatment) in type 2 diabetes. METHODS: A Medline search on published clinical trials involving sitagliptin in combined therapies was performed; additional information from published papers and abstracts to congresses on preclinical and basic science issues was also included to support the mechanistic rationale of combinations. RESULTS/CONCLUSION: In humans sitagliptin administration reduces fasting and postprandial glucose and A1c levels. Sitagliptin is as effective as glipizide (close to 0.7% mean A1c reduction), but has fewer hypoglycemic events than other oral insulin secretagogues. Since metformin reduces hepatic glucose production and increases GLP-1 release, combined therapy with sitagliptin becomes complementary and has been shown to have important additive effects. Sitagliptin combined with pioglitazone resulted in improved metabolic control when compared with pioglitazone plus placebo. Combined administration with insulin requires further studies. The weight neutral effect of sitagliptin, its glucose-dependent action (lower risk of hypoglycemia), the beneficial effects on beta-cell function and its eventual protective action on beta-cell mass makes it an excellent option for monotherapy or combined with metformin, glitazones or even sulfonylurea.
J Control Release. 2008 Jul 2; 129(1): 49-58
Sankalia JM, Sankalia MG, Mashru RC
The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.
Mutations at Arginine 352 Alter the Pore Architecture of CFTR.
J Membr Biol. 2008 Mar; 222(2): 91-106
Cui G, Zhang ZR, O'Brien AR, Song B, McCarty NA
Arginine 352 (R352) in the sixth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) previously was reported to form an anion/cation selectivity filter and to provide positive charge in the intracellular vestibule. However, mutations at this site have nonspecific effects, such as inducing susceptibility of endogenous cysteines to chemical modification. We hypothesized that R352 stabilizes channel structure and that charge-destroying mutations at this site disrupt pore architecture, with multiple consequences. We tested the effects of mutations at R352 on conductance, anion selectivity and block by the sulfonylurea drug glipizide, using recordings of wild-type and mutant channels. Charge-altering mutations at R352 destabilized the open state and altered both selectivity and block. In contrast, R352K-CFTR was similar to wild-type. Full conductance state amplitude was similar to that of wild-type CFTR in all mutants except R352E, suggesting that R352 does not itself form an anion coordination site. In an attempt to identify an acidic residue that may interact with R352, we found that permeation properties were similarly affected by charge-reversing mutations at D993. Wild-type-like properties were rescued in R352E/D993R-CFTR, suggesting that R352 and D993 in the wild-type channel may interact to stabilize pore architecture. Finally, R352A-CFTR was sensitive to modification by externally applied MTSEA(+), while wild-type and R352E/D993R-CFTR were not. These data suggest that R352 plays an important structural role in CFTR, perhaps reflecting its involvement in forming a salt bridge with residue D993.
PDA J Pharm Sci Technol. 2007 Nov-Dec; 61(6): 472-91
Shivakumar HN, Desai BG, Pandya S, Karki SS
Glipizide was complexed with beta-cyclodextrin in an attempt to enhance the drug solubility. The phase solubility diagram was classified as A(L) type, which was characterized by an apparent 1:1 stability constant that had a value of 413.82 M(-1). Fourier transform infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry and proton nuclear magnetic resonance spectral analysis indicated considerable interaction between the drug and beta-cyclodextrin. A 2(3) factorial design was employed to prepare hydroxypropyl methylcellulose (HPMC) matrix tablets containing the drug or its complex. The effect of the total polymer loads (X1), levels of HPMC K100LV (X9), and complexation (X3) on release at first hour (Y1), 24 h (Y2), time taken for 50% release (Y3), and diffusion exponent (Y4) was systematically analyzed using the F test. Mathematical models containing only the significant terms (P < 0.05) were generated for each parameter by multiple linear regression analysis and analysis of variance. Complexation was found to exert a significant effect on Y1, Y2, and Y3, whereas total polymer loads significantly influenced all the responses. The models generated were validated by developing two new formulations with a combination of factors within the experimental domain. The experimental values of the response parameters were in close agreement with the predicted values, thereby proving-the validity of the generated mathematical models.
Rev Med Liege. 2008 Feb; 63(2): 105-9
Scheen AJ, Van Gaal LF
Sitagliptin (Januvia) is the first selective antagonist of dipeptidylpeptidase-4, an enzyme that degrades glucagon-like peptide-1 (GLP-1). This hormone is mainly secreted by ileal L cells and this secretion is abnormally low in patients with type 2 diabetes. Sitagliptin increases post-meal insulin secretion ("incretin effect) by enhancing the postprandial GLP-1 response ("incretin enhancer"), in a glucose-dependent manner. It improves glycaemic control (HbA1c) in type 2 diabetic patients treated by diet alone, by metformin, by sulfonylurea, by glitazone or by a metformin-sufonylurea combined therapy. The glucose-lowering effect is similar to that of glipizide, but with the advantage of no weight gain and no hypoglycaemic episodes. The tolerance to sitagliptin is excellent. Treatment is simple, with 100 mg once daily, without need of titration or home blood glucose monitoring. In Belgium, sitagliptin is currently reimbursed in patients with type 2 diabetes not adequately controlled with diet and metformin monotherapy.
Drug Dev Ind Pharm. 2008 Mar; 34(3): 305-13
Mandal U, Pal TK
The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the United States Pharmacopeia (2000). The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.