Current Clinical Pharmacology - Volume 13, Issue 4, 2018

Background: A questionnaire is a commonly used data collection method and is a very crucial part of the research. However, designing a questionnaire can be a daunting task for postgraduate students. Methods: This manuscript illustrates the various steps required in questionnaire designing and provides an insight into the essentials of questionnaire construction and validation. Data from a questionnaire should be able to comprehend the objectives of the study; else it may lead to wrong interpretation or bias, decreased power of study and inability to generalize the study results. Conclusion: Since it is equally important to verify the usefulness of the designed questionnaire, the article briefly describes the process of psychometric evaluation of a questionnaire.

Background: In the pharmaceutical sectors, the computer plays a crucial role as a commander of all the theoretical aspects and provides a workbench to improve the overall quality of pharmaceutical research and development. The aim of this article is to provide a computational approach to the development of numerous technology of computer software in the field of clinical pharmacokinetics. The computational technique practised by clinical pharmacist and scientist with the applied knowledge and skills in dealing with clinical pharmacokinetics problems can be applied in routine clinical practices. Methods: To solve the various complicated pharmacokinetic equations and modeling of pharmacokinetic processes, various software were used like Population pharmacokinetics, Individual pharmacokinetics, Absorption, Distribution, Metabolism, and Excretion (ADME) pharmacokinetics, in - silico pharmacokinetics like Window-Based Non-linear model fitting (WinNonlin), Statistical Analysis Software (SAS), Non-linear Mixed Effects Modelling (NONMEM), PK Solution etc. Results: Various software's which was described in this paper help in the development of experimental study designs, statistical treatment of data and various simulation studies, etc. A robust software solution should be easy to use and address the three main parts of the PK-PD workflow like data management, analysis, and reporting. PK-PD software's allow researchers to predict ADME properties of new drug entity. For the study of the pharmacokinetic, the best software is WINBUGS where there is no limitation of dimensional array and size of the problem. The best software to be used for individual pharmacokinetics is T.D.M.S in which, we can apply Bayesian and least square method for curve fitting and it can be used for both linear and non-linear pharmacokinetic data. Conclusion: Various software were discussed here. This software not only help in knowing the history of the software but also help in gaining more knowledge about pharmacokinetics and pharmacodynamics simulation. Different software such as population pharmacokinetic, individual pharmacokinetic and others discussed in this article will help in the reporting and analyzing of data. The important points to be considered while selecting the software is also discussed which will help in easy accessing of software.

Cancer is one of the deadly diseases which is characterized by unchecked cell division or abnormal cell growth due to the incapability of cell cycle arrest. As the treatment for this is to kill the cancerous cells, the main challenge for scientists is to direct the cell killing to cancerous cells while leaving the normal cells unharmed. Antibody-Drug Conjugates (ADC) are one such targeted anti-cancer therapy. It is an effective drug delivery system that utilizes the targeting action of antibody along with cell death by potent cytotoxic agent, linked up with one another by a linker molecule and thus helps to reduce toxicity to non-target cells, ensure broad therapeutic window and overcome multi-drug resistance. Multiple parameters like total antibody (conjugated and unconjugated antibody), conjugated antibody, conjugated drug, unconjugated antibody and unconjugated (free) drug are needed to be analyzed to find out the behavior as well as safety and efficacy of ADCs. With 2 FDA approved drugs (Kadcylca and Adcetris) and more than 40 drugs undergoing clinical trial, this field has gained pace in recent years. Some challenges still persist in this field like reducing immunogenic response to antibodies, ensuring the ADC homogeneity and antibody-drug ratio, selection of appropriate targets, successful conjugation of drug to antibody, securing the stability of linkers in systemic circulation as well as improvement of oral bioavailability. With the advent of stable linkers, cytotoxic drugs having higher potency and better conjugation capability with the linker and antibodies having high specificity, these ADCs can overcome the limitations of cancer treatment. This review focuses on the criteria for proper construction of ADC, conjugation techniques, the target choices, the underlying mechanism of action and pharmacokinetic considerations associated with ADC.

Dietary long chain polyunsaturated fatty acids belong to omega (ω)-3, -6 or -9 series. Both experimental and clinical studies demonstrated the beneficial effect of ω -3 fatty acids of fish oil, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) against human ailments including cardiovascular diseases and rheumatoid arthritis. They are metabolized in cyclooxygenase and lipooxygenase pathways and also by cytochrome P450 isozymes. Biological importance of DHA in the development of brain and retina are well established. Recent studies highlighted the beneficial effect of ω-3 fatty acids in Alzheimer's Disease (AD) which may be attributed to their antioxidant, anti-inflammatory, antiapoptotic and neurotrophic properties. The effect was obtained by the consumption of either individual or combination of ω -3 fatty acids. The anti-inflammatory effect can be ascribed to the decreased cytokines and monocytic chemotactic protein-1 level by suppressing the nuclear factor-kappa B. Further, they inhibit cyclooxygenase-2 and nitric oxide synthase-2 activities. The antiapoptotic activity is due to the lowered Bax/Bcl ratio or caspase 3 levels. They can induce the transcription factor, nuclear erythroid factor-2 mediated expression of superoxide dismutase- 2 in order to facilitate the antioxidant effect. Both DHA and EPA can enhance the nerve growth factor level. Overall, they are beneficial to improve the cognitive function in very mild AD and major depressive disorder. Despite the beneficial effects, ω-3 fatty acids are easily prone to peroxidation. This review article discusses the recent update on the roles of ω -3 fatty acids in AD.

Background: Sodium-Glucose Cotransporter 2 (SGTL-2) inhibitors are a new class of antidiabetics, which have been approved for the treatment of patients with Type 2 Diabetes Mellitus (T2DM). Besides their beneficial metabolic effects, they exert favourable results in cardiovascular events and risk factors along with renoprotection. However, SGLT-2 inhibitors have not been yet approved as an adjunct therapy to insulin in patients with Type 1 Diabetes Mellitus (T1DM). This review aims at presenting both clinical and experimental data that reinforce the role of SGLT-2 inhibitors as adjunctive treatment in patients with T1DM along with the main restrictions of their use, namely Diabetic Ketoacidosis (DKA). Methods: We conducted a comprehensive research of the relevant literature regarding the off-label use of SGLT-2 inhibitors in clinical practice, presenting the major benefits and the potential risks. Results: SGLT-2 inhibitors are associated with improved glycemic control, reduction in body weight, and decrease in insulin dosage, along with their beneficial cardiovascular and renal effects. However, we cannot overlook the association with increased incidence of DKA events, in the presence of well known predisposing factors. Further investigation is required, in order to establish them as adjunctive treatment in those patients. Conclusion: This novel class of antidiabetics seems to be a very attractive treatment option in patients with T1DM, due to their multiple beneficial effects, but the increased risk of DKA should be taken into account.

Background: Monosodium Glutamate (MSG) is one of the most commonly used food additives for the enhancement of food taste and flavour. There are several conflicting reports of toxicity or otherwise safety of the compound, which raises a growing concern regarding the safety of monosodium glutamate as a food additive. Objective: In the present study, we sought to investigate the effect of monosodium glutamate on body weight, feed consumption, body temperature and some haematological parameters. Methodology: Twenty adult Wistar rats divided into four groups of five rats each were used for the study. Rats in groups 1, 2 and 3 were given feed thoroughly mixed with 3, 6 and 9 g of monosodium glutamate respectively for 14 days, while rats in group 4 (Control) were given only the feed for the same period of time. Body weight, temperature, feed consumption, and some haematological parameters were measured before the addition of the compound to the feed and thereafter for every 2 days for a period of 14 days. Results: Our findings indicated significant changes (P < 0.05) in the red blood cells (RBC) count, packed cell volume (PCV), as well as body temperature in all the treated groups compared to the control group. The result also revealed a significant dose-dependent increase in body weight in the groups treated with 6 and 9 g of monosodium glutamate compared to the control, the body weight correlated positively with the duration of monosodium glutamate consumption. Conclusion: The current data suggest that consumption of high doses/quantity of monosodium glutamate for a long duration of time could lead to anaemia due to a decrease in red blood cell count and packed cell volume and obesity resulting from an increase in body weight gain.

Background: Acne vulgaris is a common dermatologic disorder which results in psychological consequences. Inflammatory responses play an important role in the development of inflammatory acne lesions. Recently, many studies have demonstrated anti-inflammatory effects of statins; thus, the aim of this study was to evaluate the efficacy of oral and topical Simvastatin as adjunct therapy in the treatment of acne vulgaris. Methods: A total of 76 patients with moderate to very severe acne vulgaris, all receiving oral azithromycin (250 mg, 3 times a week, orally) and topical benzoyl peroxide gel (5%, once daily) were assigned to three groups: 1) Oral group received 20mg/day of oral simvastatin and blank solution, 2) Topical group received simvastatin 1% topical solution and oral placebo, 3) Placebo group received oral placebo and blank solution. The severity of acne was determined by global acne grading system (GAGS) at baseline and after 8 weeks of treatment. Results: Comparing the three groups showed that topical simvastatin was associated with greater decrease in acne severity as compared with those of oral and placebo groups. Moreover, the oral simvastatin appeared to be more efficacious as compared with placebo group (P value<0.001). Oral and topical simvastatin were well tolerated in almost all patients. Conclusion: Although preliminary, the results of this study showed that oral and topical statins, drugs with anti-inflammatory properties, can be considered as effective treatment for acne vulgaris as an adjunct to standard treatment. However, further studies with larger sample size, using improved formulations of topical simvastatin are needed to confirm these results.