Indonesian Journal of Pharmacy
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Comparison of Antiemetic Use Ondansetron and Metoclopramide, Evaluation of Effectiveness and Adverse Effects
Full text linkOndansetron and metoclopramide are the most often used antiemetics in clinics. According to the Indonesian National Formulary, ondansetron is exclusively approved for the prevention of nausea and vomiting caused by chemotherapy and radiation. Furthermore, Extrapyramidal Symptoms (EPS) are a side effect of metoclopramide that both patients and professionals less preferred. This research aimed to compare the efficacy and adverse effects of ondansetron with metoclopramide in adult internal medicine patients. This is a prospective cohort observational research with inclusion criteria of internal medicine patients aged ≥ 18 years who received ondansetron or metoclopramide as antiemetics. A difference test was carried out between the 2 groups on the variable effectiveness and side effects. From a total of 194 patients, 107 received IV ondansetron and 87 received IV metoclopramide. The result showed a significant reduction in nausea before and 30 minutes after drug administration in both groups (p < 0.05). There was no significant difference in effectiveness of anti-nausea and anti-vomiting in the two groups (p > 0.05). However, a significant difference was also found in headache side effects after 30 minutes between the 2 groups (p < 0.05). In conclusion, ondansetron and metoclopramide are effective in treating nausea and vomiting in adult internal medicine patients
Pharmacoeconomic Modelling In An Assessment of Acute Respiratory Disease Treatment Under Etiological Uncertainty
Full text linkThe rising of medical innovative treatment costs, combined with limited resources, have resulted in an explosion in the number of pharmacoeconomic assessments currently being conducted. In parallel with the escalating prices of novel pharmacological entities, pharmacoeconomic assessments have become increasingly relevant in decision-making. The aim of this study was to provide a theoretical justification and develop the scientific and methodological underpinnings of the efficacy of pharmacotherapy of viral infections using a mix of pharmacoeconomic analysis and mathematical modelling methodologies. The general concept of modelling was based on patient recovery or death using various pharmacotherapy technologies in the presence and absence of a viral infection, as well as using speed of recovery as a favourable prognostic sign and criterion for the effectiveness of the applied pharmacotherapy technology. Two alternative approaches were compared on the basis of decision trees, with the derivation of a universal criterion for the cost-effectiveness of introducing an additional treatment. The practical implementation of the proposed model was shown using the example of inclusion of the drug vitaglutam as an additional antiviral pharmacotherapy for patients with community-acquired pneumonia. Modelling of the normalisation of clinical and laboratory parameters combined and the duration of hospitalisation showed that the cost-effectiveness of additional pharmacotherapy for community-acquired pneumonia of viral-bacterial etiology could be reduced by an average of 29 %, based on the dynamics of normalisation of clinical and laboratory parameters compared with days of hospitalisation. This indicates that resource savings can be made by introducing this method to analyse the effectiveness of pharmacotherapy
One-Pot Synthesis and Biological Evaluation of Piperidinium-3,3'-(arylmethylene) bis-lawsone derivatives by targeting caspase-7
Full text linkCaspase-7, an effector enzyme activated by the initiator caspase-1, plays a crucial role in triggering apoptosis. It is also a significant factor in neurodegenerative conditions like Alzheimer's and Huntington's diseases. While both peptide and nonpeptide caspase inhibitors have shown promise in preclinical research, peptide inhibitors face challenges such as poor cell permeability, brief half-life, limited efficacy, and complex structures that are difficult to optimize. Additionally, they encounter bioavailability issues. Consequently, the development of nonpeptide-based caspase inhibitors remains an area of interest for researchers. Using a multicomponent reaction, eight lawsone derivatives, specifically piperidinium-3,3'-(arylmethylene) bis-lawsone, were successfully synthesized. This group included five novel compounds (2, 3, 4, 7, 8) and three previously known ones (1, 5, 6). The products were analyzed using Nuclear Magnetic Resonance (NMR) 1-2D spectroscopy and High Resolution Mass Spectrometry (HRMS), followed by an evaluation of their inhibitory activity against caspase-7. Notably, this study marks the first instance of piperidinium-3,3'-(arylmethylene) bis-lawsone being investigated for its potential to target the caspase-7 enzyme. Among the eight compounds, compound 8 demonstrated the most promising results, exhibiting an inhibitory activity of approximately 29.80% against caspase-7. This finding suggests that compound 8 could serve as a valuable fragment molecule for future development of caspase-7 inhibitors
Identification and Determination of Methylisothiazolinone and Chloromethylisothiazolinone in Cosmetics by Liquid Chromatography Tandem Mass Spectrometry
Full text linkBroad-spectrum preservatives known as isothiazolinone biocides are frequently found in cosmetic, industrial, and household products. Certain isothiazolinones (methylisothiazolinone, MIT, and chloromethylisothiazolinone, CMIT) might result in eczema, edema, or allergic contact dermatitis by dermal contact or inhalation. This study aims to develop and validate the identification and determination method of a single MIT and MIT/CMIT mixture utilizing UPLC fitted with tandem mass spectrometry quadrupole time of flight (QTOF) for various beauty products.
Several evaluations, including specificity, linearity, recovery, stability, precision, accuracy, determination of detection limit (LOD), and quantitation limit (LOQ) were conducted after some optimization processes by using LC-MS/MS QTOF. The MRM transition ion of MIT was m/z 116.0165 → 99.0091, 101.0215, and 84.9954. Meanwhile for CMIT was m/z 149.9775 → 134.9977, 86.9906, and 115.0447. MIT and CMIT were successfully distinguished and identified. The retention times of MIT and MCIT were detected at 4.53, and 5.25 min, respectively. Good selectivity was achieved by using the approach with resolution value greater than 1.5. The linearity range for single MIT was 375-1125 ng/mL, meanwhile for MIT/CMIT mixture resulted in 107.68-323.04 ng/mL for MIT and 295.36-886.08 for CMIT, respectively. Furthermore, the calibration curve approach was used to determine LOD acquired. In addition, LOQ over the LOD value was 0.00003%. These findings proved the suitability of the developed method to quantify MIT and CMIT in cosmetics. Samples of 21 cosmetic products, including soaps, shampoos, lotions, lipstick, and liquid cosmetics, from local markets and pharmacies were analysed using the developed method. Three of them were found to contain both single MIT or MIT/CMIT mixture. The technique and the data will help the Indonesian FDA to regulate the compounds used in cosmetics
Isolation of flavonoids from the Corncob of Zea mays and evaluation of their anti-oxidant and anti-tyrosinase activities
No full textOne approach to counteract the activity of the enzyme tyrosinase is by consuming a variety of foods containing high levels of antioxidant compounds. Overexpression of this enzyme can lead to degenerative diseases. Three bioactive compounds, namely Quercetin (CC-01), Kaempferol (CC-02), and Kaempferol-3-o-glycoside (CC-03), have been successfully isolated from corncobs (Zea mays). Centering our attention on the isolated compounds, we proceeded to perform in-vitro examinations on them to ascertain their antioxidant capabilities through the utilization of DPPH, ABTS, and CUPRAC-TEAC assays, employing ascorbic acid and trolox as benchmarks. Furthermore, we evaluated their anti-tyrosinase potential, employing kojic acid as a reference point. Isolation and identification of compounds from corn cobs (Zea mays) and their antioxidant and anti-tyrosinase activities through in-vitro studies. The compounds were isolated using radial chromatography and thin-layer chromatography methods. Their chemical structures were determined through ultraviolet (UV), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry. In vitro investigations included assessing antioxidant activity via DPPH, ABTS, and CUPRAC-TEAC assays, using ascorbic acid and trolox as positive controls. The anti-tyrosinase activity was also examined, employing kojic acid as a positive control for the isolated compounds derived from corn cobs. All the isolated compounds exhibit significant potential as antioxidants and inhibitors of the tyrosinase enzyme, with quercetin standing out for having the lowest IC50 value in both antioxidant and antityrosinase activities.This study may be an initial approach to define bioactive compounds contained in plants as a candidate for antioxidant and anty-tyrosinase agent in the future
Ciprofloxacin-Mefenamate Salt Preparation and Quantitative Analysis Using Green Methods
No full textSynthetizing a drug multicomponent system is an effective strategy to improve the physicochemical properties of both components. Ciprofloxacin is a BCS IV fluoroquinolone antibiotic with low solubility and permeability. Recently, this antibiotic was reported to form a salt with mefenamic acid using more modern methods and instruments. However, these instruments are still not widely accessible in developing countries. This research purposed to explore and utilize the alternative methods, which were more affordable and green, to analyze the ciprofloxacin-mefenamate salt formation. Next, the solubility of mefenamic acid in the antibiotic-antiinflammatory salt was investigated. Firstly, the multicomponent system was prepared by SDG using ethanol 98%, and the product was confirmed using PXRD, compared to the reported phase. The thermal profile was conducted using a simple melting point determination using electrothermal measurement. Next, FTIR was done to detect the salt formation, and the NMR solution also investigated the interaction in the solution phase. Another green quantitative method, spectrophotometry derivative, was developed for the solubility test performance, replacing HPLC. The results showed that the electrothermal data are similar to previously reported DSC data. Next, FTIR clearly identified the ionic interactions forming the salt through significant changes in specific bands and peak appearances, as well as NMR that may show the interaction in the solution phase. After that, the UV derivative methods were developed and validated with reliable parameters for simultaneously determining ciprofloxacin and mefenamic acid levels. The ciprofloxacin solubility increased twofold, comparable with the reported data from HPLC analysis. Meanwhile, new data showed a threefold increase in mefenamic acid solubility compared to its single component. Hence, the economist electrothermal tool, FTIR, and NMR methods effectively identified the ionic interactions in ciprofloxacin-mefenamate, which were predicted to remain stable in solution and have the potential for further development
Women’s willingness to contribute to the cost of genetic testing for germline mutations linked to breast cancer: A systematic review
No full textFemale breast cancer (BC) is one of the most common cancers in the world, with high mortality rates and substantial economic burdens. Reducing these fiscal and mortal costs can be achieved through early detection. One means of early detection is preexisting awareness of an inherited vulnerability to BC. This can be achieved through genetic testing for germline mutations. Therefore, optimizing genetic test utilization is pivotal to reducing BC deaths and costs. However, these tests are either not covered or only partially covered by insurance in most countries. Therefore, this study aimed to investigate women’s willingness to pay (WTP) for this genetic testing and the associated factors through a systematic literature review. This systematic review was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature was drawn from four databases: EBSCOhost, PubMed, ScienceDirect, and Scopus. For the analysis, WTP values were converted to their equivalent value in US 23.08 to 1,937.71, and only one study reported a co-payment rate greater than one, indicating higher WTP values than the test cost. The factors significantly correlated with WTP were sociodemographic, testing and family history, attitudes and beliefs, and perceived risk and worry. The dissemination of information about the benefits of the test and the implementation of a co-payment scheme can successfully increase WTP by making genetic testing for BC a higher priority for women. Future reviews should aim to improve the generalizability of findings
POPULATION PHARMACOKINETICS MODELING OF LEVOFLOXACIN AFTER ORAL ADMINISTRATION IN HEALTHY INDONESIAN VOLUNTEERS
No full textResearch focusing on the utility of population-based modelling in Indonesia is still minimal. This study aimed to implement the population-based approach for the pharmacokinetics profiles of levofloxacin, one of the broad-spectrum antibiotics commonly used in the treatment of infection.
A single 500 mg levofloxacin film-coated tablet was administered orally to 18 healthy volunteers (10 males and 8 females, age between 18-55 years), evaluated based on the liver and kidney function, blood and urine parameters, disease history, physical examination, blood pressure, heart rate, ECG, body weight, and the absence of viral infections (i.e., HCV, Hepatitis B, and HIV). Blood samples were periodically collected within 24 hours after dosing. Levofloxacin-plasma-concentration (Cp) was measured using a validated bioanalytical HPLC method based on selectivity, accuracy, precision, stability, LLOQ, and linearity evaluations. The population modelling of Cp time profiles used Monolix (v. 2020 R1) and NONMEM (v. 7.43). The best model was evaluated from the one-compartment and two-compartment model with and without the absorption lag-time. Moreover, the modelling was further assessed by involving and searching the appropriate covariate, including sex, age, weight, BMI, height, systolic, diastolic, pulse, respiratory rate, albumin and bilirubin concentration, SGOT, SGPT, urea concentration, total clearance, haemoglobin, lymphocytes, monocyte, eosinophile, basophil, HCT, red blood cells, and platelet.
A two-compartment model with a lag-time best describes pharmacokinetic profiles of levofloxacin. Both Monolix and NONMEM estimated similar population and individual parameter estimates of CL (Central-clearance), Vd (central-distribution-volume), Q (peripheral-clearance), V2 (peripheral-distribution-volume), Ka (absorption-rate-constant) and lag-time. Both Monolix and NONMEM confirm age and height as covariates, improving the modelling by influencing the Ka and Vd, respectively
Mechanistic insights into the modulation of lipopolysaccharide-stimulated inflammatory and oxidative stress responses by Myrmecodia platytyrea tuber ethyl acetate extract in RAW 264.7 macrophages
No full textSoutheast Asians frequently utilise Myrmecodia platytyrea (Rubiaceae) to treat inflammatory diseases, but little is known about the molecular mechanism of this herbal plant. We evaluated the effect of M. platytyrea tuber ethyl acetate extract (EAMPT) on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in RAW 264.7 cells. The total phenolic content of EAMPT were determined using the high-performance thin-layer chromatography (HPTLC). In vitro, the RAW 264.7 cells were divided into four groups: control (untreated), LPS (1 µg/mL LPS), treatment (3.75 to 60 µg/mL EAMPT plus LPS) and reference (200 µM ibuprofen plus LPS). Subsequently, cell culture samples were tested for cell viability, oxidative stress and inflammatory markers using the MTT assay, biochemical assays, ELISA, real-time qPCR and Western blot. EAMPT, with a total phenolic content of 4.15%, suppressed LPS-induced inflammation by lowering gene and protein expression of the iNOS/NO pathway and TNF-α. Furthermore, ROS levels were reduced while the HO-1 gene and protein expression increased, implying the antioxidant effect of EAMPT. The ROS-inhibitory effect was shown to be strongly correlated with its NO-inhibitory effect. EAMPT increased IL-6 gene and protein expression while no effect on the COX-2/PGE2 pathway was observed. In summary, EAMPT offers synergistic effects through dual mechanisms in an in vitro inflammation model, highlighting iNOS and HO-1 as therapeutic targets. Further research on M. platytyrea tuber's pharmacological and phytochemical characteristics may reveal its novel therapeutic potential
Physical Properties, Stability, and Biological Activity of a Combination Sunscreen Emulgel Formulation Containing Octyl Methoxycinnamate and Hexagamavunon-5: An In Vitro and In Vivo Evaluation
No full textOctyl Methoxycinnamate(OMC) has intense sunscreen activity, but susceptible to photodegradation upon exposure to UV light, leading to the formation of free radicals. The incorporation of antioxidants can mitigate UV-induced degradation and preserve OMC in its trans configuration, thereby maintaining its photoprotective efficacy. Hexagamavunon-5(HGV-5) contains phenolic hydroxyl groups and conjugated double bonds, which are key to its antioxidant activity. In this study, we develop a sunscreen emulgel formulation combining OMC and HGV-5 to improve activity, stability and safety. The Simplex Lattice Design (SLD) method was applied to optimize emulsion (Tween 80, Span 80, and Paraffin Liquid) using Design Expert (DE). The DE obtained 14 runs and testing the responses to determine the optimum formula. The optimum formula was then made into five(5) emulgel preparation. The emulgel were tested in vitro to determine percent transmission of erythema (%TE), percent transmission of pigmentation (%TP), and Sun Protection Factor (SPF) values as presenting of photostability test. The best formula of emulgel determines the in vivo irritation test, physical characterization, and stability test. Antioxidant activity HGV-5 has an IC50 180.326 µM, while the Vitamin E as a comparator, was 200.172 µM. HGV-5 has a better antioxidant activity and potential as a stabilizer agent. The DE chosen the optimum formula of emulsion were Tween 80 3.15% (v/v), Span 80 3.75% (v/v), and Paraffin Liquid 3.1% (v/v). F4 showed good photostability and obtained SPF values in the ultra protection category and %TE and %TP in the sunblock category. Referring to the storage results, the optimum formula was stable for a month. The irritation test of F4 showed that the PII value was 0 in the treatment group compared to the control group. F4 revealed that does not cause irritation, so it can be concluded that F4 is safe