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

INTRODUCTION

Diffuse cutaneous mastocytosis (DCM) is a rare and severe form of cutaneous mastocytosis which may present in the neonatal period; thus early recognition is essential. Symptoms of mastocytosis are exacerbated by mast cell degranulating agents more commonly from heat, friction, local trauma, drugs and food. This is a case of DCM presenting with bullous eruptions after immunization.

CASE REPORT

An 11-month-old boy presented with generalized erythematous to hyperpigmented macules and patches initially at birth, with progression to bullous eruptions immediately after immunization without any systemic symptoms. Biopsy revealed superficial and deep mixed cell infiltrates consisting of lymphocytes, histiocytes and numerous mast cells. Giemsa stain highlighted the metachromatic mast cell granules. Serum tryptase was elevated by 13 times (130 ug/L). The patient was prescribed oral antihistamines and topical steroids that offered good response. Avoidance of all potential triggers was instructed.

DISCUSSION

The extensive cutaneous involvement in DCM (generalized erythema, diffuse papules that develop pachyderma, darker skin, peau d’orange) are due to the diffuse infiltration of the dermis with mast cells, accompanied with an elevated serum tryptase.

Unique to this local case are exacerbations triggered by vaccination. There is literature to support evidence of vaccination reactions to pentavalent vaccine in children with DCM though the pathway associated with mast cell degranulation after immunization has not yet been specified.

It is advised that patients with DCM follow scheduled immunization guidelines with precautionary measures.

Human ; Male ; Infant: 1-23 Months ; Wounds And Injuries ; Research Report ; Pharmaceutical Preparations ; Mastocytosis, Cutaneous ; Hot Temperature

A singular medical incident can alert health officials to an emerging, if not widespread, but possibly undetected publichealth concern.

Our issue contains a remarkable case of a ruptured hepatic abscess in a 3-year-old, which turned out to be MethicillinresistantStaphylococcus aureus (MRSA) by authors Torrico and Tarnate.The concern is that the infection is communityacquired,and the patient was immunocompetent. This sounds the alarm for the occurrence of antimicrobial resistance (AMR)in the communities and calls for a response from health authorities to investigate, analyze, and propose solutions for sucha sentinel event.

We need to support these efforts and, in this issue, we publish such work from our investigators. Antimicrobial resistanceis an urgent global health concern.The impact is magnified in low to middle-income countries where health risks are high,and health infrastructure is weak. Thus, it is imperative that determinants of AMR are scrutinized to allow crafting offocused strategies to combat the problem.

The article by Dela Cruz and Hernandez on the prevalence and practices of antibiotic misuse among adult residents ofRodriguez, Rizal, contributes to this analysis.The paper reveals a disturbing prevalence of self-medication and identifiesbarriers to accessing proper health education and care. This is a global problem, and the paper from Brazil relates the observationof community pharmacists of antibiotic misuse to the rise of antimicrobial resistance.

Dela Cruz and Hernandez recommend stricter antibiotic regulation, and this falls squarely into the scope of concernof another article in this issue, the “Research Needs in Philippine Pharmaceutical Sciences: A Qualitative Perspective fromRegulatory and Clinical Research Sectors of the Pharmaceutical Industry” by Pena and co-authors.Interestingly, whiledrug registration and clinical trials were the focus of the paper, it may be a desired expansion of the regulatory reach of theindustry to temper the use of antibiotics as it is being dispensed to end users.Antimicrobial stewardship involves ethicalpromotion of use and equitable access to appropriate treatment, and these concerns require the responsible participation of thepharmaceutical industry.

Health challenges are complex. The analysis of these challenges requires surveillance of literature for sentinel events, useof community-based research to investigate phenomena, and system mapping to identify relevant sectors to improve strategyand to involve relevant stakeholders.

We support this type of scholarship, which seeks to expand the focus from isolated clinical interventions towards placinga spotlight on relevant work that will lead to impactful reform of broad health ecosystems.

Human ; Child Preschool: 2-5 Yrs Old ; Therapeutics ; Staphylococcus Aureus ; Pharmaceutical Preparations ; Research Personnel ; Health Services Needs And Demand ; Methicillin-resistant Staphylococcus Aureus ; Antimicrobial Stewardship

OBJECTIVES

This study aimed to identify problems and highlight opportunities for pharmaceutical sciences research in the Philippine pharmaceutical industry's regulatory and clinical research sectors that might have been previously overlooked or underrepresented. It identified current issues that can be addressed by research covering four areas of pharmaceutical sciences: drug design and discovery, pharmacokinetic/pharmacodynamic studies, formulation design and pharmaceutical technology, and regulatory science.

METHODS

A descriptive qualitative approach was used in this study. Data collection was facilitated by key informant interviews (KII) using a standardized interview guide with open-ended questions to identify the pharmaceutical science research needs of the specific sectors. A purposive sampling method was employed, with five key informants (KIs), including the company vice president, director, and top-level managers from different local and multinational pharmaceutical companies. ATLAS.ti software was utilized to facilitate thematic synthesis for qualitative data analysis.

RESULTS

Thirteen common themes were identified from the KIs, such as (1) incomplete development of therapeutic compounds, (2) sustainability of raw materials supply, (3) regulation of herbal medicines versus food supplements, (4) mapping disease priorities through the Philippine pharmaceutical roadmap, (5) government incentives and policies to support research, (6) technical personnel, (7) suboptimal regulatory process, approvals, and implementation, (8) gap in utilization of acquired knowledge on regulations, (9) regulatory governance, (10) passive regulatory action on counterfeit drugs, (11) PIC/S GMP version 14 adaption, (12) formulation optimization, and (13) active pharmaceutical ingredient (API) sourcing and regulation. Based on insights from the International Pharmaceutical Federation regarding anticipated hurdles in pharmaceutical sciences over the next 5-10 years, priority research needs were identified through KIs' input. Relevant action plans were developed, including the creation of research proposals to isolate, purify, and determine chemical structures of natural products, as well as analyzing recent Philippine Health Statistics to help assess the appropriateness of new drug releases for patient needs. Other action plans include forecasting future disease burdens in the country, performing toxicology studies (Health-Based Evaluation Levels/No Observed Adverse Effect Level or HBEL/NOAEL) for common generic drugs, and ensuring that research efforts are directed toward addressing the Philippine pharmaceutical regulatory and clinical research sector's most pressing needs practically and feasibly.

CONCLUSION

This study offers valuable insights into pharmaceutical sciences research and development initiatives within the regulatory and clinical research sectors in the Philippine pharmaceutical industry. These findings have the potential to catalyze transformative advancements in healthcare delivery and outcomes, positioning the Philippines for global excellence and competitiveness.

Occupational Groups ; No-observed-adverse-effect Level ; Social Control, Formal ; Patients ; Pharmaceutical Preparations

INTRODUCTION

Secondary hypertension should be suspected among young individuals and patients with recent onset of hypertension or drug-resistant hypertension. Among the causes of secondary hypertension, renovascular hypertension is well-established and correctible if diagnosed appropriately. We report the case of a young female with an unusual cause of renovascular hypertension.

CLINICAL PRESENTATION:

A 29-year-old female was admitted for elevated blood pressure and headache, unresponsive to multiple antihypertensives. The workup for secondary hypertension was mostly unremarkable. However, renal Doppler ultrasound showed elevated peak systolic velocity in the left renal artery. CT angiogram revealed an outpouching between the left gonadal and renal veins. No renal artery stenosis was found on renal angiography, but venography revealed an aneurysm between the left gonadal and renal veins. An aberrant vein draining into the inferior vena cava (IVC) and severe reflux into a dilated left gonadal vein were also noted.

MANAGEMENTCONCLUSION

This case highlights a rare cause of renovascular hypertension due to renal vein congestion from severe left gonadal vein reflux and a renal/gonadal vein aneurysm. Additional mechanisms may include external compression of the renal artery or a suction effect caused by multiple venous outflows. Regardless of the exact pathophysiology, coiling of the aneurysm and gonadal vein successfully restored normal venous return and resolved hypertension.

Human ; Female ; Adult: 25-44 Yrs Old ; Veins ; Research Report ; Renal Veins ; Pharmaceutical Preparations ; Patients ; Hypertension, Renovascular ; Hypertension ; Female ; Aneurysm

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

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*

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*