Indonesian Journal of Pharmacology and Therapy

Potential active compounds of Streptomyces sennicomposti GMY01 for antiplasmodial and antiSARS-CoV-2 revealed by targeted metabolomic and molecular docking

2025-01-14T09:50:42+07:00

Streptomyces sennicomposti GMY01 is a bacterium with huge biotechnological potential that revealed by genome mining analysis. This research aimed to investigate the potential compounds as antiplasmodial and the antiSARS-CoV-2 from the S. sennicomposti GMY01 using targeted metabolomic and in silico molecular docking. The crude extract was obtained by extraction of supernatant from fermentation product of the S. sennicomposti GMY01. The secondary metabolite profiling was obtained by using ultra-high-performance liquid chromatography (UHPLC) coupled to targeted high-performance mass spectrometry (HRMS) based on genome mining data of whole genome sequence (WGS). In silico molecular docking was performed on important target protein of P. falciparum i.e. glutathione reductase (PfGR), lactate dehydrogenase (PfLDH), phosphoethanolamine methyltransferase (Pfpmt), erythrocyte membrane protein 1 (PfEMP1) and glutathione-S-transferase (PfGST); and of SARS-CoV-2 proteins i.e. protease domain, spike glycoprotein, receptor-binding domain angiotensin-converting enzyme 2 (RBD-ACE2), 3-chymotrypsin-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp). One compound from S. sennicomposti GMY01 extract, albaflavenone was confirmed by targeted LC-HRMS. On molecular docking analysis, albaflavenone showed higher affinity than chloroquine as antiplasmodial drug and exhibited same affinity to remdesivir as antiSARS-CoV-2. Stertomyces sennicomposti GMY01 has promising biotechnological potential for drug development as antiplasmodial and anti-SARS-CoV-2 agent. Further study is needed, especially regarding in vitro testing of albaflavenone as antiplasmodial and antiSARS-CoV2.

Antiemetic prophylaxis utilization in cancer patients in a hospital in Yogyakarta Special Region

2025-01-14T09:53:06+07:00

Chemotherapy is a type cancer treatment that uses anticancer drugs to inhibit cell division and kill cancer cells. Chemotherapy can cause side effect due to normal cells damages. The study aimed to investigate the use of antiemetic prophylaxis as premedication to prevent or reduce side effects on cancer patients undergoing chemotherapy. It was a observational study with retrospective design using medical records data of cancer patients who underwent chemotherapy in a hospital in Yogyakarta Special Region during May – September 2022. The results showed the cancer patients were dominated by women (85.71%) with ages 46-65 yr (63.27%) and stage III cancer (87.76%). There were 18 types of anticancer drugs and the most widely used drugs were doxorubicin 60 mg for the moderate emetogenic category and vinorelbine 37.5 mg for the low emetogenic category. The most widely used premedication regimen was a combination granisetron 3 mg, ondansetron 8 mg, and dexamethasone 10 mg regimen (72.45%). This combination was most often used for the cancer patients with the moderate emetogenic category (39 patients or 49.4%). However, not all the cancer patients undergoing chemotherapy with the low and moderate emetogenic anticancer drugs were administered the premedication. In conclusion, doxorubicin and vinorelbine are the most widely used for cancer patients undergoing chemotherapy in the hospital. In addition, a combination of granisetron, ondansetron, and dexamethasone is widely used as premedication.

Weight growth velocity in low birth weight neonates receiving parenteral nutrition in the Neonatal Intensive Care Unit, Kandou General Hospital, Manado 2022: a retrospective observational study

2025-01-14T09:54:16+07:00

Neonates with low birth weight (LBW) have a higher risk of growth failure. To optimize their growth to target of 15-20 g/kg/d, neonates must receive adequate nutrition. Parenteral nutrition implementation is one of the approaches to provide adequate energy and nutrition to LBW neonates who can not tolerate enteral feeding. This study aims to investigate growth velocity in LBW neonates receiving parenteral nutrition in hospital settings and observe if the target growth velocity was achieved, also describes current parenteral nutrition practices in tertiary hospital settings. A retrospective observational study was conducted in the Neonatal Intensive Care Unit (NICU), Kandou General Hospital, Manado. Sample in this study were neonates with birth weight <2500 g and received only parenteral nutrition for minimum 7 d. Daily weight measurement data was collected through medical records and parenteral nutrition regimens was collected through electronic prescriptions in the Pharmacy Department. Growth velocity was assessed using two parameters, gain weight velocity and change in weight for age Z-scores (WAZ). A total of 73 neonates were used as samples. The results demonstrated that only the extremely low birth weight (ELBW) group achieved the growth velocity recommendation during parenteral nutrition, 16.17 g/kg/d. All the neonates had a negative change of weight Z-scores indicated a declining growth rate during parenteral nutrition administration. We also found lipid emulsion initiation time was later and relatively low energy intake in parenteral nutrition compared to the recommendation. Vitamin as micronutrient was not yet added in parenteral nutrition regimens. Therefore, we suggest starting lipid emulsion from the first day of parenteral nutrition and add vitamin to parenteral nutrition regimen to optimize nutrient intake in order to improve growth velocity in LBW neonates during NICU stay.

Biomarkers improving decisions making in clinical trials: explanations and examples

2025-01-14T09:54:57+07:00

Biomarkers are originate from physiological processes, medical imaging, tissues, or chemicals. They are potentially useful indicators for every type of disease and have important roles on drug discovery and development, disease progression tracking, prognosis, diagnosis, and therapy response. Biomarkers provide precision measurement results, lower bias result, also faster early warning signal. Therefore, they can be used as a basis for clinical decisions. Biomarkers found in tissues, blood, and other bodily fluids. Depend on their purpose of usage, biomarkers can be categorized of diagnostic, prognostic to predicts disease progression, pharmacodynamic to measures the effect of a drug on a biological system, and predictive to predicts response to a specific treatment. In clinical trials, biomarker can be used as basic of decisions making. Therefore, several steps required to incorporate biomarkers in clinical trials are determine roles and functions of biomarkers, choose specific test and laboratory according to purpose of trial, describe test and protocol, carry out and report analysis validation appropriate for trial, implement test in trial, and plan sustainability of biomarker uses in future research. Biomarker have been used as basis of decision making in clinical trials in phase I-IV to recruit participants or making a decision whether the trial will be terminated or continued. In this review, we outlined general explanations about molecular biomarkers, step of biomarkers incorporation in clinical trial, and examples of several studies using molecular biomarkers in clinical trial as basis of decision-making.

Pharmacogenomic of warfarin and its implication on international normalized ratio and dosing: A narrative review

2025-01-14T09:55:50+07:00

Genotype is an important factor in warfarin dosing requirements and affects the risk of excess anticoagulant use due to its narrow treatment window, high drug interactions, and frequent bleeding. The CYP2C9 and VKORC1 genotypes have a strong and consistent association with warfarin dose requirements, and the algorithms of dosing incorporating genetic and clinical information are stable warfarin dose predictions. The review article aimed to investigate the association between the genotype of CYP2C9 and VKORC1 and the current relevant dosing recommendations for warfarin in various patients. The secondary purpose was to correlate genotype with the international normalized ratio (INR). It was a narrative review of the most recent reference (observational, trial study, and RCT) on the clinical application of pharmacogenomic testing for warfarin pharmacokinetics and pharmacodynamics and its impact on INR over the last 5 yr from the PubMed and SAGEPub databases. Six studies were included in this review and showed how the genetic polymorphisms and dosage responses of different groups differed. Pharmacogenetic algorithms meet non-inferior and superior criteria for reducing dose titration compared to traditional dosing approaches, and predict actual maintenance doses well. Bleeding mostly occurred in the first mo of treatment, with no significant difference in the frequency of total bleeding between groups. Genotype-based dosing of warfarin increased the proportion of time in the therapeutic INR range (% TTR) and reduced the time to reach a therapeutic INR. Administration of CYP2C9 and VKORC1 genotypes based on warfarin may be beneficial in patients with atrial fibrillation, mechanical valve replacement, and bleeding prophylaxis for hip or knee arthroplasty. Stable warfarin doses were achieved in statistically more patients in the genotype-targeted group (47%) than in the traditional group (22%).

Optimizing rivaroxaban therapy through therapeutic drug monitoring (TDM): A review article

2025-01-14T09:56:35+07:00

Therapeutic drug monitoring (TDM) is a technique used to measure and analyze plasma drug concentrations to optimize dosages for individual patients. The goal is to maintain drug concentration within target ranges to maximize therapeutic effects and prevent side effects. Rivaroxaban, a popular direct oral anticoagulant (DOAC) could cause risks such as drug interactions and bleeding. Therapeutic drug monitoring can help mitigate these risks by ensuring personalized and appropriate dosing for the individual patient. Within 2-4 hr after a dose, rivaroxaban reaches peak concentrations due to its rapid absorption with nearly perfect absorption at a 10 mg dose. Its pharmacodynamic effects are dose-dependent. There are no significant interactions between rivaroxaban and NSAIDs like naproxen or acetylsalicylic acid. Rivaroxaban exhibits potential for clinically significant interactions with drugs that inhibit CYP3A/P-gp pathways or possess antithrombotic properties. Notably, co-administration with strong P-gp/BCRP and CYP3A4 inhibitors, such as ketoconazole and ritonavir, can lead to a substantial increase in rivaroxaban exposure.

Clinically significant of drug-drug interactions among children: a review

2025-01-20T15:18:02+07:00

Drug-drug interactions among children are a getting along concern in health care settings, specifically intensive care units, as sources of adverse drug events that may affect patient condition. Children admitted to pediatric intensive care unit are more prone to drug-drug interactions owing to the diseases and medications complexity. This condition could put the patient at high risk of harm, particularly with his critical condition, so need intense considerations from clinical practitioners to prevent adverse drug events caused by potential drug-drug interactions. This article’s review attempts to explore the important drug-drug interactions among children, including explaining the drug combination, mechanism, and related adverse drug events to help health practitioners recognize it earlier before prescribing the medication. This article’s review explored previous research results from PubMed and Google Scholar as literature resources and PRISMA flow chart as protocol for article selection process. A total of 9 articles discussed comprehensively about the type of drug combinations, mechanism of drug-drug interactions, and associated adverse drug events with significant drug-drug interactions that commonly occurred in children’s patient during the treatment. The drug-drug interaction including midazolam-phenobarbital, cannabidiol-clobazam, Paxlovid-tacrolimus, inhaled fluticasone propionate-lopinavir/ritonavir, rifampicin-warfarin, clofazimine-moxifloxacin, benzatropine-haloperidol, and enalapril-spironolactone. In conclusion, gaining a better understanding of drug-drug interactions among children will empower healthcare professionals to develop useful strategies to recognize, manage, and prevent various types of pharmacokinetic and pharmacodynamic interactions. Especially at different stages in terms of age, physiology, and complexity of the disease in children.

Current Advances in Triple-Negative Breast Cancer (TNBC) Chemotherapy: A Literature Review

2025-01-14T09:59:11+07:00

Triple-negative breast cancer (TNBC) is one of subtypes of cancer with the most associated death. With more than 20% of breast cancer patients having this subtype, an effective and safe chemotherapy is needed to ensure complete pathomorphological response. Currently, therapies for TNBC patients are divided into systemic therapy regimens for operable or non-operable diseases, with non-operable diseases mostly treated with targeted therapies such as pembrolizumab in tandem with other chemotherapy agents such as paclitaxel, gemcitabine or carboplatin. TNBC patients whom tumor is operable underwent additional step such as preoperative systemic therapy, which offers several advantages than chemotherapy alone. Neoadjuvant chemotherapy (NACT), which consist of mainly drugs from therapeutic classes such as anthracycline and taxanes, is used with limited success (23%) and decreased recurrence rates. Optimal method for treating TNBC is still lacking, therefore the need for further research regarding chemotherapy for TNBC with higher success rate and better prognosis for the patients is paramount.

Inhaled corticosteroids and incidence of pneumonia in chronic obstructive pulmonary disease (COPD) patients: A review

2025-01-14T10:01:34+07:00

Chronic obstructive pulmonary disease (COPD) is a worldwide respiratory disease that causes significant morbidity and mortality. The primary emphasis in managing COPD is on symptom control and preventing exacerbations. However, there has been ongoing discussion surrounding the safety of inhaled corticosteroids (ICS). This narrative review aimed to examine ICS influence on pneumonia in patients with COPD by consolidating findings from randomized controlled trials and observational studies. The data indicated that the utilization of ICS may be linked to a heightened susceptibility to pneumonia, with varying levels of risk reported across different ICS drugs. Regimens containing fluticasone were found to exhibit an increased susceptibility to pneumonia. The presence of a dose-dependent correlation between ICS and the incidence of pneumonia is apparent. Further investigation is necessary to clarify the fundamental principles and enhance treatment recommendations to maximize the management of COPD while minimizing the incidences of pneumonia associated with ICS.