A unique formulation of sodium bicarbonate buffered pantoprazole powder for oral suspension: perspectives from an active controlled cross-over bioequivalence study

Background:The aim was determining bioequivalence between pantoprazole buffered powder for oral suspension and pantoprazole enteric coated tablets under fasting conditions in healthy volunteers.Methods:In randomized cross-over study, participants were administered a single oral dose of pantoprazole powder as suspension 40 mg (sodium bicarbonate as buffer) or one enteric coated tablet of pantoprazole 40 mg, with240�ml of water as per the randomization schedule in each study period. Blood samples were collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 14, 16and 24hours post-dose. Plasmaconcentration of pantoprazole was determined with LC-MS and various pharmacokinetic parameters like Cmax, AUC0-t, AUC0-inf were compared between test and reference groups.Results:Amongst 41 subjects, Cmax(3752.4�84.6 vs. 3521.7�99.5 ng/ml)was achieved higher in less Tmaxtime (1 (0.28) vs. 2.3 (0.83) hrs)with test drug as compared to reference drug. The ratios of geometric least square mean and its 90% confidence interval on log transformed Cmax, AUC0-t and AUC0-inffor pantoprazole fall within the acceptance criteria of 80% to 125%. No adverse events were observed.Conclusions:Pantoprazole powder for oral suspension 40 mg (sodium bicarbonate as buffer) was well tolerated and bioequivalent with pantoprazole enteric coated tablets IP 40 mg in terms of rate and extent of absorption under fasting conditions. At same time, the shift in AUC to the left with reduction in Tmaxwith the new formulation is suggestive of faster rate of absorption.

Clinicopathological spectrum of hairy-cell leukemia: A single-center study with brief review of Indian literature

Objective: The presence of specific chemotherapeutic protocols for hairy cell leukemia (HCL) makes it essential to discriminate this entity from other lymphoproliferative disorders. Hence, awareness of the variations in clinical presentations and immunophenotypic aberrancies is requisite to ensure diagnostic accuracy. Materials and Methods: A retrospective study was carried out to analyze the clinical-pathological profile of patients with HCL diagnosed over a period of 81 months (2010–September 2017) in our institute. Flow cytometry was performed in all the patients, and further, BRAFV600E mutation analysis was performed by real-time polymerase chain reaction in a limited number of samples. Result: A total of 353 lymphoproliferative disorders were assessed during the period, of which 16 (4.5%) were diagnosed as HCL, which included 15 cases of classical HCL and single case of HCL-v. Striking male predominance was noted with a median age of 52 (range 22–90 years). 47% patients presented with pancytopenia, while 20% cases had leukocytosis. Three patients presented with bleeding diathesis in the form of melena and purpuric spots. The absence of splenomegaly was observed in 20% patients (4/15) while 2 (13.3%) cases had lymphadenopathy. Hypocellular marrow was observed in 13% cases. Bright expression of CD20/CD22 along with CD25/CD103/CD123/CD11c was noted in all the patients of classical HCL. Aberrant expression of CD23 and CD5 was seen in 33% ( n =5) and 6.7% ( n =1) cases respectively. CD200 was positive in all the 5/15 cases tested. The case of HCL–v presented with very high leukocyte count and exhibited a CD103/CD11c+ and CD123/CD25- profile. BRAFV600E, mutation was present in all the four patients tested who included patients with a hypocellular marrow and absent splenomegaly. Conclusion: HCL has characteristic profiles, yet it may exhibit unusual clinical and immunophenotypic presentations. Perspicacious use of flow cytometry and BRAFV600E mutation analysis will aid in the diagnosis in unprecedented cases

Lornoxicam efficacy in acute pain (LEAP) trial.

Parenteral non-steroidal anti-inflammatory drugs (NSAIDs) are useful agents in the treatment of postoperative pain and other acute traumatic painful conditions such as fractures. Clinical trials with lornoxicam, an oxicam derivative, document its efficacy as a potent analgesic with excellent anti-inflammatory properties in painful and or/inflammatory conditions including postoperative pain and arthritic conditions. However, there is no documentation of the efficacy and tolerability of intravenous lornoxicam in Indian patients with acute painful conditions such painful traumatic conditions requiring hospitalisation and parenteral analgesics. The present study was undertaken to evaluate the efficacy and tolerability of intravenous lornoxicam in Indian patients with postoperative pain or other acute painful traumatic conditions requiring hospitalisation and parenteral analgesia in in-office practice conditions. In this multicentric, prospective, open, non-comparative phase IV, postmarketing surveillance study patients admitted in the nursing home for either postoperative pain or painful conditions requiring hospitalisation and parenteral analgesia were enrolled in the study after obtaining their informed consent. Of the 161 patients fulfilling the selection criteria, 148 met the selection criteria and were included in the efficacy analysis. Patients were treated with intravenous lornoxicam 8 mg twice or three times daily as required for up to 3 days. Efficacy variables included changes in severity of pain scores compared to baseline values, onset of pain relief and overall global efficacy. Tolerability was assessed through monitoring of treatment-emergent adverse events, physical examination, assessments of vital signs, and overall global assessment of tolerability. Results indicated that within 1 hour of administration of intravenous lornoxicam, the mean scores of pain severity were reduced by 39.46% and by 6 hours, there was a further 52% reduction in the mean scores. Therapy with intravenous lornoxicam was associated with a faster onset of action with 15.4% patients reporting pain relief within 10 minutes and 55.9% patients within 10 to 30 minutes. Overall, global assessment of efficacy was rated as good to excellent in 95.3% of the patients. Therapy with intravenous lornoxicam was well tolerated with only 5 patients reporting adverse events such as headache (n=3) and gastritis (n=1) of mild to moderate intensity but transient. Overall, global tolerability was rated as good to excellent in 98.4% of the total cases and fair in only 1.6% of the cases. In conclusion, the results of the present study indicate that intravenous lornoxicam is a potent NSAID with an optimal efficacy/toxicity ratio and thus could be a suitable therapeutic option in the management of patients with painful traumatic conditions requiring parenteral NSAIDs and hospitalisation.

Assessment of the efficacy and tolerability of a fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg in diabetic dyslipidaemia in adult Indian patients.

Type 2 diabetes mellitus is associated with a marked increase in the risk of coronary heart disease (CHD) or stroke (by a factor of two to three compared with non-diabetic patients), and cardiovascular disease (CVD) accounts for the majority of deaths among patients with diabetes. A new fixed dose combination containing atorvastatin 10 mg + metformin SR 500 mg is being introduced in the Indian market for the treatment of dyslipidaemia in diabetic patients. The present study was therefore undertaken to assess efficacy, safety and tolerability of a fixed dose combination of atorvastatin 10mg + metformin SR 500mg in adult Indian patients with diabetic dyslipidaemia. The final protocol was approved by relevant ethics committee before the initiation of study. Informed consent was obtained from all the patients prior to enrollment in study. The total duration of study was 14 weeks including two weeks dietary run in period. Patients fulfilling the selection criteria received a single oral tablet of fixed dose combination of atorvastatin 10mg + metformin SR 500mg once daily for 12 weeks. The primary efficacy parameters were assessed by evaluating reduction in fasting and postprandial plasma glucose concentration levels at baseline and thereafter at each follow up visit at 2, 4, 8 and 12 weeks and plasma lipid profile and glycosylated Hb levels at baseline and end of study. The secondary efficacy parameters were assessed by evaluating percentage change from baseline at the end of the study (week 12) in the plasma concentration of the various lipid parameters such as total, HDL-, LDL- and very low density (VLDL)-cholesterol, triglycerides, Apo B, Apo A1, TC/LDL ratio, LDL/ HDL ratio, and percentage of patients achieving LDL-cholesterol goals as per NCEP ATP III guidelines. A total of 213 patients were enrolled in the study. Of these seven patients were lost to follow-up and considered as drop-outs. Therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg resulted in a significant reduction in the mean plasma fasting and postprandial glucose levels (35 and 38.8% respectively). There was a steep fall in the HbA1c levels from baseline levels of 8.76% to 6.74% (23.1%). There was also a significant (p < 0.05) reduction in mean total cholesterol (31.2%), LDL cholesterol (35.4%), VLDL-cholesterol (19.6%) and a significant increase HDL-cholesterol (9.5%). Thus there appeared to be trend towards reducing atherosclerosis following therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg. Mean body mass index was significantly reduced in the patients in the present study following therapy with the study drugs. The fixed dose combination of atorvastatin with metformin was well tolerated with mostly gastro-intestinal adverse events being reported in the current study. Moreover, most of the adverse events were mild to moderate in intensity and disappeared with continued treatment. In conclusion, the results of the present study suggest that, the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg is efficacious and well tolerated therapeutic modality in patients with diabetic dyslipidaemia. Furthermore this combination offers dosage convenience to the patient and by virtue of its dual mode of action is a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidaemia.

Evaluation of fixed dose combination (FDC) of telmisartan+ramipril usage in patients with micro-albuminuria and persistent hypertension: A TRIUMPH study.

Micro-albuminuria is a marker for declining kidney function and predicts increasing cardiovascular risk especially in diabetic hypertensives. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors may slow the progression of proteinuric kidney disease and thus would be valuable in these high risk patients. The present study was undertaken to assess the efficacy and tolerability of a fixed dose combination (FDC) of telmisartan and ramipril in adult Indian patients with sustained stage 2 hypertension, comorbidities and micro-albuminuria. A total 382 patients were enrolled in this multicentric, prospective open, non-comparative phase IV postmarketing surveillance study by 40 physicians in India and treated with FDC of telmisartan 40 mg+ ramipril 5 mg once daily for 12 weeks. A total 370 patients completed the study but 12 patients were lost to follow-up and considered as drop-outs. There was a significant (p<0.05) reduction in the systolic blood pressure (SBP) from 170.89 at baseline to 132. 77 mm Hg at week 12 and diastolic blood pressure (DBP) from 104.47 to 83.30 mm Hg at the end of 12 weeks therapy as well as urine albumin levels from 186.25 mg/24-hour to 62.42 mg/24-hour (66.49%) at the end of 12 weeks. Overall assessment of treatment was rated as good to excellent in 87.3% and fair in 11.4% patients. The most common adverse event reported was cough (5.2%). Results of the present study indicate that the FDC of telmisartan+ramipril brings about significant reductions in the systolic and diastolic blood pressure as well as urine albumin excretion.

An open prospective study on postmarketing evaluation of the efficacy and tolerability of diacerein in osteo-arthritis of the knee (DOK).

According to World Health Organisation osteo-arthritis is the second commonest musculoskeletal problem in the world. Diacerein has been recently introduced in India for the treatment of osteo-arthritis. In view of the ulcerogenic potential of NSAIDs and the cardiotoxicity problems associated with COX-2 inhibitors, diacerein has the potential of being a non-ulcerogenic and non-cardiotoxic alternative respectively to NSAIDs and of COX-2 inhibitors in the treatment of osteo-arthritis. The present study was, therefore, undertaken to evaluate the efficacy and tolerability of diacerein in the treatment of osteo-arthritis. A total 7923 patients with osteo-arthritis of the knee fulfilling the selection criteria were enrolled in this open-label, multicentric postmarketing surveillance study. After a wash-out period of one week, patients were treated with 50mg diacerein tablets administered twice daily for 12 weeks. The primary efficacy variable of the present study was to assess the improvement in the visual analogue scale (VAS) scores for pain. The secondary variable was improvement in patients' and physicians' global assessment of efficacy of therapy. Results indicated that over the 12-week study period, diacerein 50mg tablets provided significant and sustained reduction the VAS pain scores. At baseline, VAS scores were 6.70 +/- 1.78. By the end of the 4th week, there was a significant reduction in the mean VAS scores by 21.8% and by the end of the study the mean VAS scores were further significantly reduced by 59.9%. As per the patients global assessment of treatment, 82.3% of the patients reported good to very good improvement at the end of 12 weeks therapy with diacerein. Similar responses were also recorded by the treating patients. Thus by the end of 12 weeks therapy, according to the physicians 85.5% of the total cases treated with diacerein were rated as having good to very good improvement. Therapy with diacerein was well tolerated and only 5.44% of the patients had an adverse event after treatment with diacerein. The most common adverse events were diarrhoea (2.3%), gastritis (0.99%), nausea (0.61%), abdominal pain or discomfort (0.44%) and vomiting (0.3%). The severity of the adverse events was mild in all the cases and disappeared with continued treatment. None of the patients dropped out of the study on account of adverse events or lack of efficacy. Thus, in conclusion, the results of the present study in a large population of Indian patients indicates that diacerein constitutes a novel approach to the treatment for the short- and long-term symptomatic management in Indian patients with osteo-arthritis of the knee.

Evaluation of the efficacy, safety and tolerability of miglitol in adult Indian patients with uncomplicated type 2 diabetes mellitus.

Postprandial hyperglycaemia and spikes have deleterious effects on Insulin secretion and sensitivity. The present study was undertaken to evaluate the efficacy, safety and tolerability of miglitol 50 mg three times daily for 12 weeks in 129 patients with type 2 diabetes mellitus, inadequately managed with diet and exercise therapy alone for 3 months after obtaining their written informed consent. The primary efficacy variables were per cent change from baseline at week 12 in fasting and postprandial plasma glucose concentrations and glycosylated haemoglobin (HbA(1C)) levels. After treatment at the end of 12 weeks mean reduction in fasting plasma glucose levels was 35.7% and 44.33% in postprandial plasma glucose levels while the mean HbA(1C) was significantly reduced by 0.88% (p<0.05). Total cholesterol, HDL, LDL and TC/HDL ratio did not showed any significant change but a non-significant reduction in triglyceride levels was observed in some patients. The mean body mass index was reduced non-significantly by 8% from baseline values. A total 19.5% patients treated with miglitol reported adverse events like flatulence, abdominal pain, nausea/vomiting, diarrhoea and dyspepsia. Only one patient reported hypoglycaemia. The results of the present study indicate that miglitol reduces fasting and postprandial plasma glucose levels, Improving glycaemic control, which is reflected in a reduced HbA(1C) level in patients with type 2 diabetes mellitus. It could be a useful first-line therapy in patients with type 2 diabetes mellitus inadequately controlled by diet alone and as adjuvant therapy in patients who are inadequately controlled with diet and sulfonylureas.