Determination of in-vitro Equivalence of Paracetamol Tablets

Bioequivalence studies are the usually accepted method to determine the therapeutic equivalence of two drugproducts. Because in-vivo bioequivalence studies are time consuming and expensive to conduct, majorregulatory authorities have introduced biowaivers for some selected medicines belonging to BCS class 1 andIII drugs. Comparative dissolution tests are used in biowaiver procedure to waiver the bioequivalencerequirement. We performed this study to see whether two brands of paracetamol tablets are bioequivalentusing the in-vitro methodology. In the first stage of this research study, British Pharmacopeia 2012 qualitytests were performed on the two selected paracetamol tablet products to determine whether they arepharmaceutically equivalent. In the second stage in-vitro equivalence of the two products was determinedusing the biowaiver testing procedure given by the World Health Organization. Dissolution profiles weregenerated at pH values, 1.2, 4.5 and 6.8. Results were compared through two model independent methods,difference factor (f1) and similarity factor (f2). The two paracetamol tablet products tested, complied with allthe quality requirements of the British Pharmacopeia 2012. For the two products, the difference factor (f1)was below the 15 and similarity factor (f2) was above the 50 in all dissolution test conditions. These resultsconfirm that the two products are pharmaceutically equivalent. The test product is also bioequivalent to thereference product in-vitro, and therefore they can be interchangeable during clinical use. This study showsthat in-vivo bioequivalence testing can be waived using the in-vitro method, for some pharmaceuticalproducts such as paracetamol tablets.KEYWORDS: Paracetamol tablets, Biowaivers, Dissolution profile

Sex Difference in Risk Factors, GRACE Scores, and Management among Post-Acute Coronary Syndrome Patients in Sri Lanka

Objective. To assess sex-based differences in the prevalence of risk factor, their management, and differences in the prognosis among acute coronary syndrome (ACS) in Sri Lanka. Methods. Patients diagnosed with ACS were recruited from hospitals throughout the island. The Joint European Societies guidelines were used to assess recommended targets for coronary heart disease risk factors, and the GRACE score was used to assess the post-ACS prognosis. Age-adjusted regression was performed to calculate odds ratios for men versus women in risk factor control. Results. A total of 2116 patients, of whom 1242 (58.7%) were men, were included. Significant proportion of women were nonsmokers; OR = 0.11 (95% CI 0.09 to 0.13). The prevalence of hypertension (p<0.001), diabetes (p<0.001), and dyslipidemia (p=0.004) was higher in women. The LDL-C target was achieved in a significantly higher percentage of women (12.6%); OR = 0.33 (95% CI 0.10 to 1.05). When stratified by age, no significant differences were observed in achieving the risk factor targets or management strategies used except for fasting blood sugar (p<0.05) where more men achieved control target in both age categories. Majority of the ACS patients had either high or intermediate risk for one-year mortality as per the GRACE score. In-hospital and 1-year mean mortality risk was significantly higher among men of less than 65 years of age (p<0.05). Conclusions. Smoking is significantly lower among Sri Lankan women diagnosed with ACS. However, hypertension, diabetes, and dyslipidemia were more prevalent among them. There was no difference in primary and secondary preventive strategies and management in both sexes but could be further improved in both groups

Determination of in-vitro equivalence of paracetamol tablets

Bioequivalence studies are the usually accepted method to determine the therapeutic equivalence of two drugproducts. Because in-vivo bioequivalence studies are time consuming and expensive to conduct, majorregulatory authorities have introduced biowaivers for some selected medicines belonging to BCS class 1 andIII drugs. Comparative dissolution tests are used in biowaiver procedure to waiver the bioequivalencerequirement. We performed this study to see whether two brands of paracetamol tablets are bioequivalentusing the in-vitro methodology. In the first stage of this research study, British Pharmacopeia 2012 qualitytests were performed on the two selected paracetamol tablet products to determine whether they arepharmaceutically equivalent. In the second stage in-vitro equivalence of the two products was determinedusing the biowaiver testing procedure given by the World Health Organization. Dissolution profiles weregenerated at pH values, 1.2, 4.5 and 6.8. Results were compared through two model independent methods,difference factor (f1) and similarity factor (f2). The two paracetamol tablet products tested, complied with allthe quality requirements of the British Pharmacopeia 2012. For the two products, the difference factor (f1)was below the 15 and similarity factor (f2) was above the 50 in all dissolution test conditions. These resultsconfirm that the two products are pharmaceutically equivalent. The test product is also bioequivalent to thereference product in-vitro, and therefore they can be interchangeable during clinical use. This study showsthat in-vivo bioequivalence testing can be waived using the in-vitro method, for some pharmaceuticalproducts such as paracetamol tablets.KEYWORDS: Paracetamol tablets, Biowaivers, Dissolution profile

Additional file 1: of Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications

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Effects of Zinc supplementation on serum lipids: a systematic review and meta-analysis

Zinc is a mineral that plays a vital role in many biological processes and plays an important role in insulin action and carbohydrate metabolism. It may also have a protective role in the prevention of atherogenesis. Numerous studies have evaluated the effects of Zinc supplementation on serum lipids in humans and have demonstrated varying results. We systematically evaluated the literature and performed a meta-analysis on the effects of Zinc supplementation on serum lipids. A five staged comprehensive search of the literature was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus for studies published before 31st December 2014. All controlled clinical trial in humans, that included a Zinc supplement intervention, either alone or in combination with other micronutrients and evaluated effects on serum lipids (total cholesterol [TC], triglycerides [TG], LDL cholesterol [LDL-c] and HDL cholesterol [HDL-c]). A meta-analysis of selected studies was performed using RevMan v5.3. The Jaded scale was used to assess the methodological quality of the trials included in the systematic review. A total of 24 studies were included in Meta analysis, which included a total of 33 Zinc interventions, in a total of 14,515 participants in the Zinc intervention or control group. The duration of Zinc supplementation ranged from 1 month to 7.5 years. The dose of elemental Zinc supplemented ranged from 15–240 mg/day. The pooled mean difference for TC between Zinc supplemented and placebo groups from random effects analysis was −10.92 mg/dl (95 % CI: −15.33, −6.52; p < 0.0001, I(2) = 83 %), while for HDL cholesterol it was 2.12 mg/dl (95 % CI: −0.74, 4.98; p = 0.15, I(2) = 83 %). The pooled mean difference for LDL-c between Zinc supplemented and placebo group from random effect analysis was −6.87 mg/dl (95 % CI: −11.16,-2.58; p < 0.001, I(2) = 31) and for TG it was −10.92 mg/dl (95 % CI: −18.56, − 3.28; p < 0.01, I(2) = 69 %). In conclusion, Zinc supplementation has favourable effects on plasma lipid parameters. Zinc supplementation significantly reduced total cholesterol, LDL cholesterol and triglycerides. Therefore it may have the potential to reduce the incidence of atherosclerosis related morbidity and mortality

Core Prescribing Indicators and the Most Commonly Prescribed Medicines in a Tertiary Health Care Setting in a Developing Country

Irrational prescribing is common, especially in developing countries. It is important to identify the magnitude of irrational use, to take necessary steps to promote rational prescribing. We identified core prescribing indicators and commonly prescribed medicines at ward settings (IW) and outpatients’ clinics (OPC) in a tertiary care hospital in Sri Lanka. A descriptive cross-sectional study was carried out at IW and OPC settings. Prescriptions were obtained from 5 major specialties (Clinical Medicine (CM), Gynaecology and Obstetrics (GO), Paediatrics, Psychiatry, and Surgery). The WHO core prescribing indicators were used to describe the pattern of prescribing, and the most commonly prescribed medicines were identified. A total of 1,318 prescriptions were analyzed. The five most commonly prescribed medicines were paracetamol (31.0%), omeprazole (20.6%), folic acid (18.3%), atorvastatin (16.2%), and salbutamol (15.3%). The average number of medicines per encounter was 4.8 ± 3.6 (IW: 5.7 ± 4; OPC: 3.8 ± 2.8; p<0.001), with the highest IW (7.8 ± 4.2) and OPC (7.8 ± 2.7) values were from CM, being significantly higher than all other disciplines (p<0.05). Percentage encounters with an antibiotic or an injection was 26.4% and 30.1%, respectively, with IW being significantly higher than OPC (p<0.001). Percentage of medicines prescribed by generic name and from the essential medicine list (EML) was 90.1% and 91.1%, respectively, with no significant IW and OPC difference. In conclusion, a high degree of polypharmacy was noted. The use of injectable medicines, prescribing from the EML, and generic name prescribing was satisfactory; however, overall rational prescribing needs further improvement. Further investigation into the degree of rational prescribing associating it with clinical information will be important

Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

Introduction: Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 FNx013, FNx014 and FNx0114 variants associated with the loss of enzyme function; CYP2D6 FNx0110 and FNx0117 variants with reduced enzyme function; and CYP2D6 FNx012 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs. Objective: The objective of this study was to determine the prevalence of CYP2D6 FNx012, FNx013, FNx014, FNx0110, FNx0114 and FNx0117 variants in the main ethnic groups in the Sri Lankan population. Materials and Methods: A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods. Results: The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 FNx012: 37%, 41.6% and 37.9%; CYP2D6 FNx013: 60.3%, 45% and 30%; CYP2D6 FNx014: 21.6%, 6.6% and 8.3%; CYP2D6 FNx0110: 40%, 35% and 44%. CYP2D6 FNx0114 and FNx0117 variants were not identified. Conclusion: CYP2D6 FNx013, FNx014 and FNx0110 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6FNx014, which is reported to be a Caucasian variant was also found in all three ethnic groups

Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial

Abstract Background Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19. Trial design and methods A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups. Results Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 − 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000–65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load. Conclusion Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms. Trial registration number SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021