Background An extracorporeal membrane oxygenation (ECMO) device represents an additional functional body compartment, potentially impacting vancomycin pharmacokinetics. Objectives This systematic review aimed to: (1) provide a comprehensive summary of vancomycin population pharmacokinetics (Pop-PK) in critically ill patients receiving ECMO and; (2) associate the findings with clinical practices and dosing recommendations. Methods PubMed, Embase and Google Scholar databases were searched for vancomycin non-linear mixed-effects modelling Pop-PK studies in ECMO patients (inception-May 2024). Standardized, pre-tested and pilot-tested tools were used for quality assessment and data extraction utilizing triangulation. Summary measures included typical values for vancomycin pharmacokinetic parameters, influential covariates, and associated interindividual and residual variabilities. Results Seven studies reporting an approximate total of 1600 vancomycin blood concentrations (range: 33–433 concentrations per study) collected from 215 patients (range: 11–93 patients per study) were included. Pop-PK models fitted three-compartment (n = 1), two-compartment (n = 5), or one-compartment (n = 1) models. Various modalities [venovenous-ECMO (n = 6); venoarterial-ECMO (n = 5), centrifugal-pump (n = 6), roller pump (n = 1)] and age groups were reported [pediatrics (n = 2); adults (n = 6)]. Vancomycin clearance and central volume of distribution (V1) ranged between 0.0579–4.32 L/h and 0.13–3.32L/kg, respectively. Relatively high between-subject variability (BSV) exists (clearance: 0.1%–77%; V1: 0.33%–94.8%). Models failed to explain maximally 19.4% of the overall variations, successfully explaining at least 80.6% of the variabilities in vancomycin disposition in ECMO. Age and body weight were significant covariates on clearance and V1. Additionally, glomerular filtration rate, serum creatinine, creatinine clearance, and use of dialysis were significant covariates on clearance. Clinical status-related covariates (i.e., acute physiology and chronic health evaluation II (APACHE-2) score, sequential organ failure assessment (SOFA) score, presence of shock) and ECMO modality-related covariates (pump type/flow rate, ECMO mode) were not significant covariates in the final clearance and V1 models. Conclusion This work comprehensively compiles up-to-date population-approach-based dosing simulations and pharmacokinetic models of vancomycin in ECMO, with special focus on influential predictors of vancomycin disposition to guide clinical dosing decisions. Relatively small sample sizes of patients were reported, a limitation that needs to be addressed in future large-scale studies. Observed BSV mandates therapeutic drug monitoring using Pop-PK models and parameters summarized in this work. Large-scale studies are needed to explore unexplored covariates, resulting in more informative dosing nomograms.
A simple and reliable HPLC method was developed and validated for determination of rofecoxib in bovine serum albumin microsphere. The analyses were performed on a C18 column (150 x 4.6 mm, 5 μm particle size) at room temperature with UV detection at 272 nm. The mobile phase was composed of acetonitrile-0.1% o-phosphoric acid solution in water (1:1, v/v) mixture, and flow rate was set to 1 mL/min. The method was validated according to the international guidelines with respect to stability, linearity range, limit of quantitation and detection, precision, accuracy, specificity, and robustness. The detection and quantification limit of the method were 1.0 μg/mL and 2.5 μg/mL, respectively. The method was linear in the range of 2.5–25 μg/mL with excellent determination coefficients (R2 >0.99). Intra-day and inter-day precision (<1.76% RSD) and accuracy (<0.55 % Bias) values of the method also fulfilled the required limits. It was concluded that the developed method was accurate, sensitive, precise, and reproducible according to the evaluation of the validation parameters. The applicability of the method was confirmed for in vitro quantification of rofecoxib in bovine serum albumin microspheres.
Acemetacin (ACIN) is a poorly water-soluble nonsteroidal anti-inflammatory drug, which limits its effectiveness in topical therapeutic applications. This s
İyi yönetilen ve planlanan varfarin tedavisi önemli bir antikoagülan seçenek olmuştur ve antikoagülasyon sağlayıcılarının rehberliği optimum sonuçları elde etmeyi kolaylaştırmıştır. Karmaşık farmakokinetik ve farmakodinamik profiline rağmen, varfarin, günümüzde de en yaygın kullanılan oral antikoagülan ajanlardan biridir. Bu ajan ile optimal antikoagülasyona ulaşmak, birçok gıda ve ilaç etkileşimi nedeniyle klinik olarak zordur. İlaç tedavisi her bir hastaya uyacak şekilde özel olarak uyarlanmalı ve uygun şekilde birlikte kullanılabilecek bitkisel ilaçların ve diğer ilaçların etkinliğini artırabileceği veya ilaç toksisitesini azaltabileceği mutlaka göz önünde bulundurulmalıdır. Uygunsuz antikoagülasyon kontrolü, hastaları sırasıyla aşırı ve yetersiz koagülasyon nedeniyle kanama veya tromboembolik komplikasyon riskinde artışa maruz bırakabilmektedir. Özellikle K vitamini alımındaki dalgalanmaların, varfarin ile tedavi edilen hastalarda antikoagülasyon derecesi üzerinde önemli bir etkisi bulunmaktadır. Ek olarak, çeşitli diyet takviyeleri ve bitkisel ürünlerin kullanımındaki artış da antikoagülan seviyelerinde istenmeyen sonuçlara yol açabilmektedir. Bu derlemenin amacı, en sık kullanılan ilaçlar, besin ve diyet takviyelerinin varfarinin farmakokinetiği üzerindeki etkilerini tartışmaktır.
Purpose: For superficial pain, nonsteroidal anti-inflammatory medications (NSAIDs) offer sufficient analgesia, particularly in cases of mild to severe dull pain. Diclofenac potassium is one of the most preferred drugs in this group, but its low water solubility and high permeability due to its BCS II class classification makes it a challenging active substance in the formulation process. The aim of this study was to develop and evaluate in vitro of emulgel formulations containing diclofenac potassium. Materials and Methods: All substances used in the formulation development process were substances in conformity with pharmacope specifications. Emulgel formulations containing diclofenac potassium were prepared and evaluated in terms of pH, conductivity, rheological properties, viscosity, drug release rate and stability. Results: The method developed and validated for the determination of the active ingredient resulted in a good linear relationship that was established between the peak areas and the concentrations (2.5-40 μg /mL) of diclofenac potassium with the determination coefficient (R2) which equals to 0.9999. F1, F2, F3 and F4 formulations were found to be stable at the end of the 1st and 3rd month when evaluated with the amount of active substance, pH and rheological properties at different temperatures and conditions. Formulations F2 and F4 are more viscous than other formulations F1 and F3. The initial pH values of all prepared formulations were found to be compatible with the skin. When the reological properties of the formulations were studied, they were determined by examining the calculated R2 values of the Herschel-Bulkley reological type (R2 values of F1, F2, F3 and F4 formulations respectively were 0.999045, 0.999301, 0.999650, 0.999631). In the drug release rate studies, the release of active substance from F2 and F4 formulations continued until the 6th hour and reached plateau values. Conclusion: Diclofenac potassium emulgel can be used as an antiinflammatory analgesic agent for topical drug delivery.