Gout is the most common inflammatory arthritis among Filipinos, characterized by hyperuricemia leading to mono- sodium urate crystal deposition and an ensuing inflammatory response. Though typically a disorder of middle- aged and older adults, tophaceous gout presenting before the age of 30 is rare and suggests aggressive disease progression. Allopurinol, a first-line urate-lowering therapy, is generally effective but may cause rare, potentially life-threatening adverse reactions such as allopurinol hypersensitivity syndrome (AHS). Febuxostat, a non-purine xanthine oxidase inhibitor, is an alternative for patients intolerant to allopurinol. Although hypersensitivity reactions to febuxostat are extremely rare, isolated case reports document their occurrence in both patients with prior AHS and in allopurinol-naïve individuals. Hypersensitivity to both agents is exceedingly uncommon and presents a major therapeutic challenge. In such cases, febuxostat desensitization, conducted in collaboration with allergy specialists, may permit a viable solution to safely reintroduce urate-lowering therapy and prevent further disease progression. This case report describes a patient with young-onset, tophaceous gout who developed severe hypersensitivity reactions to both allopurinol and febuxostat — an unusual and challenging therapeutic dilemma. The case highlights the need for individualized management strategies, including the consideration of drug desensitization, in patients with limited urate-lowering options.

Human ; Male ; Adult: 25-44 Yrs Old ; World Health Organization ; Therapeutics ; Specialization ; Solutions ; Research Report ; Pharmaceutical Preparations

Drug-induced sleep endoscopy (DISE) is used for directly visualizing sites of obstruction among patients with obstructive sleep apnea (OSA). Owing to the scarcity of data, there is still no consensus on the anesthetic regimen for conducting pediatric DISE.

This paper presents a 5-year-old patient who underwent DISE using an opioid-sparing regimen with dexmedetomidine and propofol infusion.

Simultaneous dexmedetomidine and propofol infusion is a promising opioid-sparing regimen for pediatric DISE.

Human ; Male ; Child Preschool: 2-5 Yrs Old ; Endoscopy ; Propofol ; Dexmedetomidine ; Sleep Apnea, Obstructive ; Anesthetics ; Apnea ; Consensus ; Paper ; Patients ; Pharmaceutical Preparations ; Research Report ; Sleep ; Sleep Apnea Syndromes ; World Health Organization

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

BACKGROUND

The existence of counterfeit medicines has been a long-standing global public health concern. In the Philippines, Republic Act No. 8203 Section 3 provides a definition of counterfeit medicines, outlines prohibited acts, and states liabilities and penalties of concerned parties. The Philippine legal definiti on of counterfeit medicine needs to be aligned to what is widely accepted by the international community and to update its scope to prevent varied interpretations due to a mix in the categories of “counterfeit medicines.”

OBJECTIVE

This qualitative narrative policy review aims to generate evidence on counterfeit and falsified medicines from grey literature and recent publications in order to propose recommendations for updating the legal framework to address specifically “falsified” medical products.

METHODS

An online search was performed to identify relevant literature that discussed counterfeit medications. A review of narrative textual evidence from grey literature was conducted including extraction of data on the proliferation of fake, unregistered, and substandard medicines from published news articles and reports for the past six years. A review of published literature was also conducted to supplement findings from aforementioned reports and articles.

RESULTS

Literature search revealed that the presence of counterfeit medicines remains prevalent in the country despite the enactment of RA 8203. Counterfeited products include over-the-counter medicines, prescription medicines, and vaccines. The classification of counterfeit medicines in grey literature, including news articles and FDA advisories, are aligned with the WHO definitions.

CONCLUSION

There is a clear need to update the regulatory framework on counterfeit medicines which would entail revisiting RA 8203 to amend the definition of counterfeit medicines and other related provisions in alignment with the WHO definitions.

Human ; Philippines ; Drugs ; Medicine ; Pharmaceutical Preparations

Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
Nanomedicine ; Humans ; Nanoparticles/chemistry* ; Pharmaceutical Preparations/chemistry* ; Animals ; Drug Carriers/chemistry*

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

This study investigated the mechanism of action of Scutellariae Radix-Coptidis Rhizoma(SR-CR) in intervening in non-alcoholic fatty liver disease(NAFLD) in rats based on lipidomics. Thirty-six SD rats were divided into a control group, a model group, SR-CR groups of different doses, and a simvastatin group, with six rats in each group. Rats in the control group were fed on a normal diet, while those in the remaining groups were fed on a high-lipid diet. After four weeks of feeding, drug treatment was carried out and rats were sacrificed after 12 weeks. Serum liver function and lipid indexes were detected using kits, and the pathomorphology of liver tissues was evaluated by hematoxylin-eosin(HE) staining and oil red O staining. Changes in lipid levels in rats were detected using the LC-MS technique. Differential lipid metabolites were screened by multivariate statistical analysis, and lipid metabolic pathways were plotted. The changes in lipid-related protein levels were further verified by Western blot. The results showed that compared with the control group, the model group showed increased levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.01), and decreased levels of γ-glutamyl transferase(γ-GT) and high-density lipoprotein cholesterol(HDL-c)(P<0.01), which were significantly recovered by the intervention of SR-CR. HE staining and oil red O staining showed that different doses of SR-CR could reverse the steatosis in the rat liver in a dose-dependent manner. After lipidomics analysis, there were significant differences in lipid metabolism between the model group and the control group, with 54 lipids significantly altered, mainly including glycerolipids, phosphatidylcholine, and sphingolipids. After administration, 44 differential lipids tended to normal levels, which indicated that SR-CR groups of different doses significantly improved the lipid metabolism level in NAFLD rats. Western blot showed that SR-CR significantly decreased TG-synthesis enzyme 1(DGAT1), recombinant lipin 1(LPIN1), fatty acid synthase(FASN), acetyl-CoA carboxylase 1(ACC1), and increased the phosphorylation level of ACC1. These changes significantly decreased the synthesis of TG and increased the rate of its decomposition, which enhanced the level of lipid metabolism in the body and finally achieved the lipid-lowering effect. SR-CR can improve NAFLD by inhibiting the synthesis of fatty acids and TG.
Rats ; Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Scutellaria baicalensis ; Drugs, Chinese Herbal/therapeutic use* ; Pharmaceutical Preparations ; Rats, Sprague-Dawley ; Liver ; Triglycerides/metabolism* ; Cholesterol ; Diet, High-Fat ; Azo Compounds

Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.
Humans ; Extracellular Vesicles ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stem Cells ; Pharmaceutical Preparations

OBJECTIVE: To study the effects of the neuro-microenvironment on the mass of mitochondria in hematopoietic stem and progenitor cells (HSPC), and to understand the potential mechanisms how nerve regulates HSPC. METHODS: 6-hydroxydopamine (6-OHDA) and capsaicin were used to interfere with the function of sympathetic nerve and nociceptive nerve in mitochondria-GFP reporter mice, respectively. The fluorescence intensity of GFP in bone marrow and spleen was measured by flow cytometry. The GFP median fluorescence intensity (MFI) of HSPC in normal bone marrow and spleen was analyzed and compared. The changes of the mitochondrial mass in HSPCs in each group after denervation were compared. RESULTS: Hematopoietic stem cells (HSC) had the highest mito-GFP MFI in steady-state (49 793±1 877), and the mito-GFP MFI gradually decreased during the differentiation of HSCs. Compared with control group, pharmaceutical nociceptive denervation significantly increased the mito-GFP MFI of bone marrow multipotent progenitor-1 (MPP1, 50 751±420 vs 44 020±510) and LKS^- cells (15 673±65 vs 13 979±103); pharmaceutical sympathetic denervation significantly reduced the mito-GFP MFI of bone marrow LKS⁺ cells (21 667±351 vs 29 249±973). CONCLUSION Sympathetic and nociceptive nerves can regulate the mass of mitochondria in HSPC and affect the function of HSPCs.
Animals ; Mice ; Hematopoietic Stem Cells ; Bone Marrow/metabolism* ; Cell Differentiation ; Mitochondria ; Pharmaceutical Preparations/metabolism*

Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.
Humans ; Carcinoma, Hepatocellular/pathology* ; Consensus ; East Asian People ; Liver Neoplasms/pathology* ; Pharmaceutical Preparations ; Infusions, Intra-Arterial/methods* ; Antineoplastic Agents/therapeutic use* ; Drug Therapy, Combination/methods*