WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Numerous retrospective analyses have shown the utility ofin vitrosystems for predicting potential drug–drug interactions (DDIs).• Prediction of DDIs fromin vitrodata is commonly obtained using estimates of enzymeK_i, inhibitor and substrate concentrations and absorption rate for substrate and inhibitor.WHAT THIS STUDY ADDS• Using a generic approach for all test compounds, the findings from the current study showed the use of recombinant P450s provide a more robustin vitromeasure of P450 contribution (fraction metabolized,f_m) than that achieved when using chemical inhibitors in combination with human liver microsomes, for the prediction of potential CYP3A4 drug–drug interactions prior to clinical investigation.• The current study supported the use of SIMCYP®, a modelling and simulation software in utilizing thein vitromeasures in the prediction of potential drug–drug interactions.AIMS: The aim of this study was to explore and optimize thein vitroandin silicoapproaches used for predicting clinical DDIs. A data set containing clinical information on the interaction of 20 Pfizer compounds with ketoconazole was used to assess the success of the techniques.METHODS: The study calculated the fraction and the rate of metabolism of 20 Pfizer compounds via each cytochrome P450. Two approaches were used to determine fraction metabolized (f_m); 1) by measuring substrate loss in human liver microsomes (HLM) in the presence and absence of specific chemical inhibitors and 2) by measuring substrate loss in individual cDNA expressed P450s (also referred to as recombinant P450s (rhCYP)) The fractions metabolized via each CYP were used to predict the drug–drug interaction due to CYP3A4 inhibition by ketoconazole using the modelling and simulation software SIMCYP^®.RESULTS: Whenin vitrodata were generated using Gentest supersomes, 85% of predictions were within two‐fold of the observed clinical interaction. Using PanVera baculosomes, 70% of predictions were predicted within two‐fold. In contrast using chemical inhibitors the accuracy was lower, predicting only 37% of compounds within two‐fold of the clinical value. Poorly predicted compounds were found to either be metabolically stable and/or have high microsomal protein binding. The use of equilibrium dialysis to generate accurate protein binding measurements was especially important for highly bound drugs.CONCLUSIONS: The current study demonstrated that the use of rhCYPs with SIMCYP^®provides a robustin vitrosystem for predicting the likelihood and magnitude of changes in clinical exposure of compounds as a consequence of CYP3A4 inhibition by a concomitantly administered drug.

(1) Background: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Tobramycin were prepared using a solvent-evaporation method. (2) Methods: The NPs were coated with low molecular weight chitosan (LMWC) to enhance the mucoadhesiveness of PLGA-NPs. The following w/w ratios of tobramycin to LMWC were prepared: control (0:0.50), F₀ (1:0.25), F₀.₅ (1:0.5), and F₁ (1:1). (3) Results: The results showed that the size of the particles increased from 220.7 nm to 575.77 nm as the concentration of LMWC used in the formulation increased. The surface charge was also affected by the amount of LMWC, where uncoated-PLGA nanoparticles had negative charges (−2.8 mV), while coated-PLGA NPs had positive charges (+33.47 to +50.13 mV). SEM confirmed the size and the spherical homogeneous morphology of the NPs. Coating the NPs with LMWC enhanced the mucoadhesive properties of the NPs and sustained the tobramycin release over two days. Finally, all NPs had antimicrobial activity that increased as the amount of LMWC increased. (4) Conclusion: In conclusion, the formulation of mucoadhesive, controlled-release, tobramycin-LMWC-PLGA nanoparticles for the treatment of P. aeruginosa in cystic fibrosis patients is possible, and their properties could be controlled by controlling the concentration of LMWC.

Steroids are compounds widely available in nature and synthesized for therapeutic and medical purposes. Although several analytical techniques are available for the quantification of steroids, their analysis is challenging due to their low levels and complex matrices of the samples. The efficiency and quick separation of the HPLC combined with the sensitivity, selectivity, simplicity, and cost-efficiency of fluorescence, make HPLC coupled to fluorescence detection (HPLC-FLD) an ideal tool for routine measurement and detection of steroids. In this review, we covered HPLC-FLD methods reported in the literature for the steroids quantification in clinical, pharmaceutical, and environmental applications, focusing on the various approaches of fluorescent derivatization. The aspects related to analytical methodology including sample preparation, derivatization reagents, and chromatographic conditions will be discussed.

This paper describes a set of fast and selective high performance liquid chromatography (HPLC) methods coupled to electro-spray ionisation linear ion

There are health concerns associated with increased folic acid intake from fortified food and supplements. Existing analytical methods, however, which can be employed to carry out epidemiological and bioavailability studies for folic acid involve laborious sample preparation and/or lengthy chromatographic analysis. In this paper we describe a simple, rapid, and sensitive high-performance liquid chromatography–electrospray ionisation-tandem mass spectrometry (HPLC–ESI-MS/MS) method for determination of unmetabolised folic acid in human plasma using folic acid-d4 as an internal standard. The method required only a simple sample preparation step of protein precipitation and had a total run time of 3.5 min, which is the shortest run time reported to date for HPLC–MS/MS method employed for quantifying folic acid in plasma. The analytes were separated on a C18 column (3 µm; 50 × 3.00 mm) using an isocratic mobile phase consisting of ammonium acetate (1 mM)-acetic acid-acetonitrile (9.9:0.1:90, v/v/v). The method was fully validated in terms of accuracy, precision, linearity, selectivity, recovery, matrix effect, and stability. The short run time and the minimal sample preparation makes the method a valuable tool for performing high-throughput analyses. To demonstrate the applicability of the method in real conditions, it was applied successfully in a bioavailability study for the determination of unmetabolised folic acid levels in vivo in human plasma after oral administration of folic acid.

Cardiovascular diseases are described as disorders of heart and vessels that involve stroke and coronary heart diseases. People in the Middle East converged to complementary medicine as an economic alternative to expensive healthcare services. Crataegus monogyna Jacq. (Lindm.) Rosacea is among the most commonly used herb for the treatment of declining cardiac performance, hypertension, and arrhythmias. Previously, we had shown that Crataegus Spp. (Hawthorn) extract increased the tendency of bleeding among patients undergoing coronary artery bypass grafting. Herein, the effects of Crataegus Spp. extract on oxidative stress, cardiac and hematological parameters were evaluated in Sprague Dawley rats. Male rats were randomly assigned into four groups. Group 1 served as control while groups 2–4 served as the experimental groups and were administered extract at doses of 100, 200, and 500 mg/kg. All the doses were given orally once/day and the treatment was continued for three weeks. Hawthorn treatment resulted in a significant decrease in the liver thiobarbituric acid reactive substances level in a dose-dependent manner compared to the control (1.258 (3, 24); P < 0.0001). We found a significant increase in the cardiac antithrombin III among hawthorn treated group compared to the control (4.18 (3, 24); P < 0.0001). On the other hand, hawthorn treatment decreased significantly the liver factor-X level (0.1341 (3, 22); P < 0.0001), while no significant changes were seen in soluble-platelet endothelial cell adhesion molecule-1 (P-value = 0.0599). In conclusions, hawthorn extract possesses an antioxidant effect and blood-thinning properties. Hence, we recommend attention when using this herbal extract with other anticoagulation and/or antiplatelet drugs or undergoing major cardiac surgery.