Journal of Pharmacy and Pharmaceutical Sciences最新文献

Background/objectives: Optimal nutrition in very low birth weight (VLBW) infants is associated with improved clinical outcomes. When parenteral nutrition (PN) with a marketing authorisation is not appropriate, hospital pharmacies can prepare more suitable PN preparation. This corresponds to standard preparations (i.e., available at any time with a fixed composition) or individualised ones (i.e., available after a period of prescription, preparation, and pharmaceutical control). In France, 12 standard formulas to be compounded were proposed by a national consortium in 2018. The objective of the present study was to evaluate whether individualised PN preparations ordered in our hospital are substitutable by one of the 12 standard formulas.

Methods: All PN prescriptions for VLBW infants made in 2021 in our hospital were retrospectively extracted. For each prescription, the theoretical intakes that an infant would have received if a standard preparation had been administered were calculated. Standard and individualised preparations were compared using the Mann-Whitney U test for each component. Secondly, the relative difference between the expected intakes and effectively intakes was calculated for each component.

Results/discussion: Over the study period, 1708 prescriptions were identified (corresponding to 1708 PN individualised preparations). Most infants were extremely low birth weight infants. Based on the methods of comparison, none of the 12 standard formulas fitted with targeted intakes achieved with individualised PN preparations ordered, whereas prescriptions did fit with international guidelines.

Conclusion: The study highlights how it is difficult to establish nationally standard PN formulas for VLBW infants; the development of local standard formulas seems therefore relevant.

Objective: Despite the antioxidant, anti-inflammatory, and anti-cellular-aging activities of urolithin A (UroA), a naturally occurring postbiotic, its high lipophilicity hampers its pharmaceutical application. To overcome this limitation improving its stability and bioavailability, submicron emulsions (S-EMs) were designed.

Methods: Nineteen formulations (S-EM 1/S-EM 19) were prepared by two different methodologies. S-EMs were characterized evaluating macroscopical appearance and size distribution by photon correlation spectroscopy (PCS). One selected S-EM was loaded with UroA and characterized by PCS, transmission electron microscopy (TEM), small angle x-ray scattering (SAXS) and Fourier-transform infrared spectroscopy (FT-IR). Z potential, pH and syringeability were evaluated. UroA entrapment was studied efficiency by ultrafiltration and HPLC, while in vitro release by dialysis. Cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) viability test on primary dermal human fibroblasts. The anti-inflammatory activity of S-EM-UroA was evaluated at 3, 6, and 24 h post-injection using the carrageenan-induced paw edema model in male C57BL/6 mice, and compared with UroA suspension and unloaded S-EM.

Results: The preformulative study enabled to select method and composition for S-EM preparation. S-EM 18 was selected for UroA loading (SEM-UroA), due to mean diameter, zeta potential, pH and syringeability suitable for intraperitoneal administration. The loading of UroA (0.2 mg/mL) did not influence S-EM physicochemical features, while maintaining technological properties for 3 months. In vitro drug release showed a biphasic profile, 2.35-fold faster in the case of SEM-UroA compared to the drug suspension. In vitro studies revealed absence of cytotoxicity at concentrations up to 5 µM. In vivo studies, conducted as a first step in assessing the potential of S-EM-UroA, demonstrated a dose-dependent anti-inflammatory effect. Specifically, S-EM-UroA at 2 mg/kg reduced paw edema at 24 h (p < 00.5; One-Way ANOVA followed by Tukey's test), and at 4 mg/kg significantly reduced edema at all time points (p < 0.01), whereas the UroA suspension or S-EM had no effect on carrageenan-induced paw edema at any time point.

Conclusion: These findings underscore the potential of UroA loaded S-EM as an effective delivery system, demonstrating its superiority over simple UroA suspensions in enhancing the systemic anti-inflammatory effects of the postbiotic.

Zaleplon (ZLP) is a commonly used sedative-hypnotic drug that has low oral bioavailability because of its poor water solubility and extensive hepatic metabolism. This study aimed to encapsulate ZLP into spanlastic nanovesicles to enhance its bioavailability via transdermal delivery. Using Span 60 and Tween 80, ZLP-loaded spanlastics were fabricated using thin film hydration technique according to 3² full factorial design. In the applied design, the influence of formulation variables on vesicle size, entrapment efficiency, and cumulative drug amount released over 24 h was investigated, leading to the identification of the optimal formulation. The optimized spanlastics were nanosized, spherical vesicles measuring 297.2 ± 8.17 nm, with an encapsulation efficiency of 65.75 ± 3.28% and a 24-hour drug release rate of 76.44 ± 5.66%. FT-IR studies revealed no significant chemical interactions between ZLP and the excipients used. HPMC K100M transdermal patches loaded with the optimized ZLP-spanlastics were formulated utilizing solvent casting technique. The patches were smooth and elastic with uniform drug content, ranging from 92.65 ± 2.54 to 96.12 ± 1.57%. The steady-state flux (Jss) of the spanlastic transdermal patch (ZLP-SP1) across rabbit skin was over 3.62 times higher than that of the control transdermal patch, indicating a significant enhancement in drug permeation. The investigated transdermal patches were stable under accelerated conditions with non-irritating properties. The in-vivo studies have shown that the pharmacokinetic parameters of ZLP oral suspension and ZLP-SP1 are significantly different, with the relative bioavailability of ZLP-SP1 being 2.681%. Therefore, these fabricated transdermal patches could be effectively used to treat insomnia.

A biowaiver generally refers to the request to waive an in vivo bioequivalence study. A biowaiver may be granted not only based on the Biopharmaceutics Classifications System (BCS) but also for many immediate-release dosage forms based on pre-defined criteria. The current paper summarises the results from a survey of the biowaiver requirements for cutaneous/topical products (topical solutions, gels, suspensions, ointments, and creams), ear/otic and ophthalmic solutions and suspensions, enemas in solution and suspension, and vaginal solid dosage forms and suppositories defined by the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the results from the survey indicates that there is a trend towards convergence when the dosage forms are less complex; however, the most common approach used by each of the participants was a case-by-case approach given that most participants do not have well-defined guidelines to support all possible scenarios. Notwithstanding the differences, disseminating information is the first step towards regulatory convergence regarding biowaivers for certain dosage forms and will be useful for pharmaceutical companies currently developing generic medicinal products for countries represented by IPRP participants.

Objective: Tacrolimus-mycophenolic acid (MPA)-prednisolone immunosuppression remains the first-line management of kidney transplantation. Despite this, a switch to low-dose tacrolimus in combination with an mTOR inhibitor may be inevitable in some patients due to various factors. This study aims to identify the reasons and factors influencing the switch of tacrolimus-MPA to other combination immunosuppressive agents among kidney transplant recipients (KTRs).

Methods: This retrospective observational cohort study included adult KTRs between year 2011-2019 at the two main kidney transplant centers in Malaysia. Demographic data, clinical, laboratory and medication information were collected. Multiple logistic regression was used to determine factors associated with the initial switch of tacrolimus-MPA immunosuppressive therapy.

Results: From the 257 KTRs studied, 81 KTRs had their immunosuppressive agents switched from tacrolimus-MPA-prednisolone immunosuppressive regimen, with majority (96.3%, n = 78) switching to everolimus, an mTOR inhibitor in combination with low-dose tacrolimus. The average time switch was 125.8 ± 100.9 days. The main reasons for the initial switch include unresolved transaminitis (n = 15, 18.5%), cytomegalovirus (CMV) infection (n = 13, 16.0%) and BK virus (BKV) infection (n = 10, 12.3%). In the multiple logistic analysis, Malay ethnicity (P < 0.001), KTRs without post-transplant hypertension (P = 0.004) and KTRs with BKV infection (P < 0.001) were predictors for the initial switch of tacrolimus-MPA-prednisolone immunosuppressive therapy.

Conclusion: Early identification of factors associated with the switch may prepare healthcare professionals for KTRs risk stratification, allowing ample time for appropriate optimization of tacrolimus-MPA-prednisolone immunosuppressive therapy based on individual patient's needs. This can possibly be a cost-effective alternative to switching to mTOR inhibitors for improved transplant outcomes.

[This corrects the article DOI: 10.3389/jpps.2024.13210.].

Pharmacogenomic (PGx) research investigates how an individual's genetic make-up impacts their drug metabolism. PGx testing can therefore inform therapeutic decision-making, especially as compelling evidence develops over time to substantiate its clinical and personal utility across a range of therapeutic areas. PGx biomarker CYP2D6, in particular, is widely implicated in drug metabolism and across several therapeutic areas. Real-world evidence (RWE) derived intentionally using electronic health record (EHR) and insurance claims data presents an opportunity to explore clinical-behavioral outcomes and implementation barriers and facilitators for PGx testing in real-world clinical settings. In this systematic review, we explored these areas with a focus on PGx biomarker CYP2D6, investigating drug-gene pairs with strong evidence (Level A, Final classification by the Clinical Pharmacogenetics Implementation Consortium [CPIC]). Across 25 studies that met our study inclusion criteria, nine (9) drug-gene pairs that met the CPIC Level A, Final, strong evidence category for CYP2D6 were described. Overarching qualitative themes across studies were 1) variation in CYP2D6 biomarker testing and interpretation, and 2) PGx test implementation and data considerations. CYP2D6-drug pairs were reported across four therapeutic areas (analgesia [n = 21], psychiatry [n = 17], oncology [n = 7], gastroenterology [n = 6]) with the two most researched drugs being codeine (n = 21) and tramadol (n = 18). Six (6) of 25 articles reported PGx clinical outcomes, considered to be a "measurable change in symptoms, overall health, ability to function, quality of life, or survival outcomes" in relation to PGx testing. Special EHR and claims data considerations for future work include but are not limited to addressing inconsistent phenotype categorizations (i.e., natural genotype versus phenoconversion); lack of reliable racial, ethnic, and genetic ancestry data within EHR and claims data sources; and data inoperability issues between PGx test results and EHRs.

Introduction: Tiotropium, a long-acting muscarinic antagonist, is commonly employed for the maintenance treatment of chronic obstructive pulmonary disease (COPD) and asthma. While its efficacy has been validated through numerous randomized controlled trials, safety concerns in real-world post-marketing settings necessitate further evaluation.

Aim: This study aimed to analyze the adverse events (AEs) associated with tiotropium reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to identify potential safety signals.

Methods: A retrospective analysis was conducted on adverse reaction reports related to tiotropium in the FAERS database from the first quarter of 2004 to the fourth quarter of 2024. The AE names in the FAERS database were systematically classified using the Preferred Terms (PTs) and System Organ Classes (SOCs) provided by the latest version of the Medical Dictionary for Regulatory Activities (MedDRA 27.1). After deduplication, a combination of methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), was employed for disproportionality analysis.

Results: A total of 129,763 AE reports related to tiotropium were included in the analysis, affecting 65,045 patients. These reports encompassed 27 different SOC categories, identifying 264 AEs associated with tiotropium. After excluding certain AEs deemed clinically insignificant, the most common AEs reported were dyspnea (n = 8,600), cough (n = 2,440), and pneumonia (n = 2080). The AEs exhibiting the highest signal strength included aggravated dyspnea (ROR: 162.04), hoarseness (ROR: 43.42), and aggravated chronic obstructive airway disease (ROR: 43.17). Additionally, we identified potential risks not mentioned in the instructions (United States Prescribing Information and the Canadian Product Monograph), such as epiglottic cancer, halo vision, and malignant lung tumors.

Conclusion: This study offers a more comprehensive understanding of tiotropium by uncovering previously unreported adverse reactions. Physicians should take these newly identified adverse reactions into account when prescribing this medication.

Object: The development of cognitive-enhancing drugs from Ginkgo biloba extract is actively pursued worldwide. This study compares the chemical compositions of different G. biloba extracts and their formulated drugs, highlighting the distinguishing characteristics and potential benefits of optimized G. biloba extract, EGb 761^®.

Methods: We analyzed three G. biloba extracts and fifteen formulated drugs using HPLC, principal component analysis, and LC-MS/MS to identify key compositional differences. Molecular docking analysis was conducted to evaluate the binding affinity of the key component with a target protein involved in cognitive enhancement. CYP inhibition assays were performed on selected extracts and their derived products to examine drug-drug interactions.

Results: EGb 761^® and its formulated drugs displayed a unique composition, characterized by a significantly higher level of protocatechuic acid (PCA). PCA demonstrated strong interactions with the M₁ receptor, acetylcholinesterase, glycogen synthase kinase-3, which are the key targets for cognitive enhancement. CYP inhibition assays indicated that EGb 761^® and the drugs derived from EGb 761^® had lower inhibitory activity compared to other samples.

Conclusion: The high PCA content in EGb 761^® may contribute to cognitive benefits. With low CYP inhibition, it suggests minimal interference with drug metabolism, highlighting its potential as a safer cognitive enhancer. Ultimately, this study indicates that the composition of EGb 761^® can be effectively leveraged for its pharmacological benefits.