Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice

Study Design: Randomized control trail

Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014

Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartanfor four weeks after induction of diabetes

Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation [r-value, 0.92] with significant p-value [0.015] in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive

Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone

Protective effect of melatonin against methotrexate induced hepatotoxicity in mice

Objective: To evaluate protective role of melatonin against methotrexate induced hepatotoxicity

Study Design: Randomized controlled trial

Place and Duration of Study: Department of Pharmacology Army Medical College, duration of the study was, from Apr to Aug 2016

Material and Methods: Eighteen mice were randomly divided into three groups [n=6]. Group [Gp]-1 received normal saline. Gp-2 received single intraperitoneal injection of methotrexate [MTX] while Gp-3 received melatonin along with MTX. Blood samples for measuring serum alanine amino transferase [ALT], aspartate amino transferase [AST] and alkaline phosphatase [ALP] along with liver samples for hepatic histological examination were taken after 24 hours of last dose

Results: In Gp-2 MTX there was significant rise in serum ALT, AST and ALP as compared to its control gp [p<0.05]. There was significant attenuation of serum ALT, AST and ALP with protective Gp-3 [MTX + Melatonin] when compared with Gp-2 [p<0.05]. The histopathological findings in the liver of mice of Gp-2 MTX showed mild fatty changes which were markedly reduced in mice treated with melatonin along with MTX though minimal inflammation was seen

Conclusion: Melatonin has hepatoprotective potential when administered along with methotrexate

Determination of S- and R-warfarin enantiomers by using modified HPLC method

Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical. Method was validated according to ICH guidelines and was found to be sensitive, reliable and less time consuming. For both enantiomers, LLOQ was 12.5ng/mL. The CV% and accuracy for method were in the range of 0.8-14.6% and 92-107% respectively. The recoveries for both enantiomers were in the range of 86-103.8%. Blood samples were collected from 170 stable patients taking warfarin and S- and R-warfarin levels were determined by this method. Majority of subjects were found to have S/R-warfarin ratio of about 1:2 as reported in previous studies due to rapid clearance of S-enantiomer than R-enantiomer. However individual subjects data was suggestive of presence of slow metabolizers of S-warfarin leading to altered S/R ratio. Previous studies have also pointed out CYP2C9 polymorphism being responsible for such inter-individual differences in S-warfarin metabolism. So plasma warfarin S/R ratio may serve as a useful phenotypic test for CYP2C9 polymorphism

Frequency of different disorders requiring warfarin therapy and its outcome in terms of dosage and INR value in Pakistani population

To determine the frequency of different disorders requiring warfarin therapy and to see the target INR and warfarin dose requirement in Pakistani population. Descriptive study. The study was carried out at Armed Forces Institute of Cardiology [AFIC] Rawalpindi, Military Hospital Rawalpindi and National Institute of Cardiovascular Diseases [NICVD], Karachi, Pakistan from October 2010 to March 2012. Stable patients taking warfarin therapy were recruited after detailed medical history, physical examination and laboratory tests. The demographic and clinical data of individuals were entered in a pre-structured proforma. Patients suffering from hepatic and renal disease, any co-morbid disease or taking any concurrent medication or diet which would have affected warfarin therapy, were excluded. Data was analyzed using SPSS version 20.0. A total of 607 stable patients fulfilling the eligibility criteria, participated in the study. There were 297 [48.9%] male and 310 [51.1%] female patients. The mean age was 37.93 +/- 12.23 years [range 18-65 years]. The most common indication for warfarin therapy was valvular heart diseases [93.4%] followed by atrial fibrillation [2.3%] whereas other indications for warfarin use are less commonly seen in our study population. Patients had mean international normalized ratio [INR] value of 2.3 +/- 0.8 [range 1.5-3.5]. Mean daily dose of warfarin calculated in 607 patients was 5.62 +/- 1.98 mg with the range of 0.36-15 mg whereas mean weekly dose was 39.36 +/- 13.8 mg with the range of 2.5-105 mg. In Pakistani population the most common indications for warfarin use are valvular heart diseases followed by atrial fibrillation. The mean INR values were within recommended range of 2-3. The mean daily dose observed in long-term therapy is comparable to the empirical dose of 5 mg routinely started in clinical practice

Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects

Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen [100mg] either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC[0-t], AUC[0- Infinity], C[max], T[max], t[1/2] Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC[0-24], AUC[0- Infinity] and C[max] for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value [p-0.05]. ANOVA gave p-values which were more than the specified value [p-0.05] for sequence, subject, period and formulation. Test formulation of flurbiprofen [tablet Flurso] was found to meet the criteria for bioequivalence to branded product [tablet Ansaid] based on pharmacokinetic parameters