Pioglitazone

A method was developed for simultaneous estimation of Metformin HCl, pioglitazone HCl and
glibenclamide in pure and tablet dosage form by using methanol as a solvent. Metformin HCl, pioglitazone HCl
and glibenclamide show absorbance maxima at 237 nm, 270 nm and 230 nm respectively. Shimadzu UV 1700,
capable of multicomponent analysis, was used for quantitation. This method is based on a multiwavelength
spectroscopic method. Validation study reveals that the methods are specific, accurate, precise, and reproducible.
All three drugs obey Beer's law in the concentration ranges used for the methods. Validation studies are
statistically significant as all the statistical parameters are within the acceptance range (% COV< 2.0 and S.D. <
2.0) for both accuracy and precision study. High recovery and low % COV reveals the reliability of the method for
quantitative study of three drugs in tablet formulation. The methods are simple, rapid accurate, precise,
reproducible, and economic and can be used for routine quantitative analysis of Metformin HCl, pioglitazone HCl
and glibenclamide in pure and tablet dosage form.
Keywords: Multi-wavelength spectroscopy, Metformin Hydrochloride, Pioglitazone Hydrochloride and
Glibenclamide

Background of the study: The prime objective of any work in pharmaceutical plant, whether in production or quality control is to manufacture product of requisite quality at the lowest possible cost. Validation is attaining and documentation of sufficient evidence to give reasonable assurance that the process under consideration does and what it purports to do. Methods: In the present study, process validation studies were carried out for a bilayer tablet containing extended release Metformin, Pioglitazone and Glimepiride as per the protocol. The parameters used during the studies were dispensing, sifting, mixing, preparation of granulating solution, granulation, drying and sizing, lubrication (flow property & assay lubricated granules), compression (weight variation, hardness, thickness, friability, content uniformity), labeling and packing. Results and Discussion: The samples collected at different stages were analyzed using UV and HPLC method as per protocol. The results were found to be within the acceptance criteria. Conclusion: From the validation studies carried out, it was observed that no modification was required in present manufacturing process. The method requires further validation only when there is change in raw materials or equipment or process.

To compare the bioequivalent parameters of 30 mg pioglitazone tablets manufactured locally (Glista) and originally (Actos). A randomized, single dose, two-treatment, two-period, two-sequence crossover study was conducted Twenty-four healthy volunteers were recruited at Siriraj Clinical Research Unit. Each subject received a 30 mg pioglitazone tablet of both formulations with at least a week washout period Blood samples were collected over 48 h after the oral administration. The plasma fractions were analyzed for pioglitazone using a liquid chomatography-mass spectrometry (LC-MS/MS). Twenty-four volunteers enrolled in the present study. Pharmacokinetic parameters were determined using the non-compartment model. The 90 percent confidence intervals of the mean ratios (test/reference) of Cmax (86.2687-113.7313%), A UC0--&gt;t(85. 7139-114.2861%) and AUC0--&gt;infinity (81.7820-118.2180%) fell within the acceptable range (80-125%) for bioequivalent eligibility. Both preparations were wel...

This study was performed to see how pioglitazone at low doses could affect blood biomarkers related to atherosclerosis and aging. The effects of an add-on treatment with pioglitazone (15 mg for males and 7.5 mg for females) for 6 months were assessed in 24 outpatients (12 males, 12 females) with type 2 diabetes aged ≥ 70 years. As doses of sulfonylurea were reduced in 10 patients, no significant differences in HbA1c and glucose levels were seen. After the treatment, serum levels of HDL cholesterol, arachidonic acid (predominant in males), and high-molecular-weight adiponectin significantly increased. The level of dehydroepiandrosterone sulfate significantly decreased. No significant changes were seen in those of small dense LDL cholesterol, high-sensitivity C-reactive protein, and amyloid beta peptides 1–40 and 1–42. There was a slight but significant increase in body weight, but apparent adverse effects were not observed. In conclusion, pioglitazone at low doses increased serum adi...

Medicaid covers a high-risk population typically underrepresented in clinical trial data and largely absent in observational studies of real-world cardiovascular risks associated with thiazolidinediones (TZDs), such as pioglitazone and rosiglitazone, which are used to manage type 2 diabetes. In November 2013, the FDA removed prescribing restrictions for rosiglitazone in light of new evidence that rosiglitazone did not increase the risk of heart attack compared with standard type 2 diabetes medications. Further investigation is needed to elucidate whether the risk of heart failure (HF) associated with TZDs may be exacerbated in the Medicaid population. To determine the relative risk of incident HF in patients initiating rosiglitazone, pioglitazone, and metformin therapy in a Medicaid population. We retrospectively examined claims data for patients with type 2 diabetes enrolled in Maryland State Medicaid and managed care or fee-for-service programs between July 2005 and June 2010. Pat...

Objective: To study the effect of HPLC purified herbal anti-hyperglycemic active compound (FIIc) isolated from the fruit pulp of Eugenia jambolana in diabetic rats.
Methods: 24 male wistar rats were taken and diabetes was induced in group B, C and D rats (n = 6 each) by injecting Streptozotocin at a dose of 45 mg/kg of body weight 15 minutes after Nicotinamide at a dose 230 mg/kg body weight intraperitoneally after overnight fasting. Active compound (FIIc) was given to group C and Pioglitazone to group D at dose of 20 mg/kg of body weight orally for 4 weeks respectively. Glycemic and lipid profile, protein tyrosine kinase activity and serum DPP-4 levels were measured and compared between all the 4 study groups.
Results: Significant Improvement in body weight, glycemic profile, dyslipidemia and tyrosine kinase activity (4.90 ± 1.28 U/mg protein) were observed in FIIc treated rats at week 4 of the study compared to diabetic control rats. Serum DPP-4 levels (26.41 ± 0.43 pg/ml) were also found to be decreased in FIIc treated rats at week 4 of the study compared to diabetic control rats. This is possibly due to increased serum insulin levels and increased insulin sensitivity after treatment with active compound FIIc.
Conclusion: FIIc significantly reduced hyperglycemia and dyslipidemia by inhibiting DPP-4 levels and improves insulin sensitivity by increasing protein tyrosine kinase activity and serum insulin levels.

Objective: The Angiotensin-II receptor blocker telmisartan and sulfonylurea glimepiride may have clinical usefulness as partial agonists of PPARg. We investigated additive and antagonistic effects among combinations of telmisartan, glimepiride, and the Thiazolidinedione (TZD) selective PPARg agonist pioglitazone on transcriptional activity of PPARg.
Materials/Methods: The receptors of pCMX-PPARg and pCMX-RXR, and PPRE-Luc reporter gene were transfected into CV1 cells, and treated with following agents, and luciferace assay was performed. Moreover, mammalian two-hybrid assay was done using GAL4 responsive reporter tk-MH100(UAS)×4-Luc and the chimeric receptor GAL4-PPARg.
Results: Telmisartan increased transactivation of PPARg dose-dependently. Activation by telmisartan 10 μM was 58.8% of that by pioglitazone 10 μM. Glimepiride also increased transactivation of PPARg dose dependently. Activation by glimepiride 10 μM was 49.8% of that by
pioglitazone 10 μM. Addition of telmisartan 5 μM significantly enhanced transactivation by glimepiride 10 and 50 μM. Moreover, addition of pioglitazone 0.5 μM significantly enhanced transactivation by glimepiride 10 and 50 μM. Mammalian two-hybrid assay showed additive effect between glimepiride and telmisartan on binding of SRC-1 to PPARg. On the other hand, addition of glimepiride 10 and 50 μM reduced transactivation by pioglitazone 5 μM to 74% and 70%, respectively.
Conclusion: Partial agonists of PPARg additively enhanced transactivation by other agonists, whereas high concentration of partial agonists reduced transactivation by full agonist antagonistically.

Background:  Pioglitazone  is  widely  prescribed  oral
hypoglycaemic  thiazolidinediones  acting  through  Peroxisome
Proliferators  Activated  Receptor  gamma  (PPAR  ƴ)  as  agonist.
Apart  from  potent  anti-hyperglycaemic  action  by  improving
insulin sensitivity, it also has positive effects on lipid metabolism
and endothelial function. Controversies about use of Pioglitazone
have  been  raised  with  regard  to  risk  of  bladder  cancer.  Hence recently drug was banned in India, but again ban was revoked for its use with special precautions. So there is a lot  of debate about benefit  to  risk  ratio  of  this  drug.  With  this  background  we  are presenting  a  case  of  carcinoma  of  urinary  bladder  developed  in type  2  diabetes  mellitus  (T2DM)  patient  who  was  receiving Pioglitazone for glycemic control.
Case presentation: A  65 year old man was admitted to our centre
for tumor in urinary bladder. He was diagnosed as a case T2DM 8
year’s  back  at  his  village  and  started  therapy  with  Metformin.
After  2  years  Pioglitazone  was  added  for  glycemic  control.  He received Pioglitazone in combination with Metformin for 6 years and  then  diagnosed  urinary  bladder  cancer.  First  we  shifted  him from Pioglitazone to Mixtard Humiinsulin therapy. We  managed him  by  transurethral  resection  of  bladder  tumour  followed  by  6 cycles  of  intravesical  Mitomycin  40  mg  weekly  chemotherapy regimen.  After  completion  of  total  treatment  he  is  in  remission period for 11 months.
Conclusion:  To  study  long  term  safety  of  Pioglitazone,  large
population based prospective studies are required. But till that time physicians should pay careful attention to assess the possibility of bladder cancer in patients receiving Pioglitazone.

We optimized and validated a rapid, simple, and sensitive HPLC assay for pioglitazone concentration in human plasma and studied the stability of pioglitazone under various clinical laboratory conditions. Pioglitazone and lansoprazole as internal standard (IS) were extracted from 1 ml plasma sample spiked with 4.0 μg in 160 μl mobile phase) as follows: 4.0 ml of tert. butyl methyl ether was added and the sample was vortexed for 5 min then centrifuged for 10 min at 6000 rpm at room temperature. The organic layer was transferred to a clean tube and dried under a gentle stream of nitrogen at 40 oC, and the residue was reconstituted in 250 μl mobile phase. After centrifugation at 3500 rpm for 2 min, the supernatant was transferred into auto-sampler vials and 100 μl were injected into the HPLC system. Pioglitazone and IS -Pak C18 steel column, using a Guard Pak pre-column module with Nova-Pak C18 4-μm insert, with a run time of 7 min. The mobile phase consisted of a mixture of 0.01 M diba...

Objective: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. Case Summary: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient’s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient’s ALT and AST serum concentrations had normalized....

Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5µg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenyle...