Arzneimittel-Forschung-Drug Research最新文献

The main objective of this study was to investigate the pharmacokinetic characters of eszopiclone (CAS: 138729-47-2) after single and multiple-dose oral administration in healthy adult Chinese volunteers.In single-dose study, 12 subjects were given oral administrations of 1.5, 3 and 6 mg eszopiclone in an open-label, randomized, crossover fashion. In multiple-dose study, 8 subjects were given 3 mg eszopiclone once daily consecutively for 7 days. Blood samples were collected over 24 h and plasma eszopiclone were determined using a validated liquid chromatography/mass spectrometry (LC/MS/MS) assay. The safety and tolerability of eszopiclone was evaluated by adverse events recording, physical examination, laboratory testing, vital signs, and 12-lead ECG findings.The main pharmacokinetic parameters of eszopiclone after single-dose administration were as follows: doses of 1.5, 3 and 6 mg; Cmax of 18.08±4.65, 38.29±15.41 and 76.38±23.34 ng/ml; Tmax of 0.94±0.39, 1.04±0.63 and 1.08±0.51 h; AUC0-24 of 110.90±23.06, 227.36±62.41 and 504.10±140.13 ng*h/ml; elimination half-lives of 5.84±1.03, 5.53±1.91 and 6.17±1.23 h. After multiple-dose administration, the steady-state levels of eszopiclone were achieved by the 4th day, and the main pharmacokinetic parameters were Css_max at 33.43±5.63 ng/ml and AUCss (0-24) at 263.30±51.21 ng*h/ml. The most common adverse event was bitter or abnormal taste. All the adverse events were judged as mild to moderate and resolved without any medication.The pharmacokinetic character of eszopiclone is linear and dose-proportional over the range of 1.5-6 mg. The systemic exposure does not accumulate with once-daily administrations. Eszopiclone appears to have good safety and is well tolerated.

Chalcones constitute one of the major classes of natural products belonging to the flavonoid family, and they have been reported as having a range of important therapeutic activities, including some chalcones are effective as antimicrobial agents. Currently, the search for new structures with antimicrobial activity has been intensified due to the emergence of many strains resistant to antibiotics currently used to treat infectious diseases.3 chalcone series (amino, acetamido and nitrochalcones) were prepared (23 compounds) and evaluated for their antimicrobial and cytotoxic potential. The effects of substituents on their respective activities also was evaluated.The results showed that 4 aminochalcones (2, 4, 8, 9), 3 acetoamidochalcones (10, 14, 18) and 3 nitrochalcones (20, 22, 23), exhibited antifungal effects. The aminochalcones were more toxic than the acetamidochalcones, while the nitrochalcones did not present any toxic effect. It was verified that there seems to be structure-activity correlation in some electron-donating and withdrawing substituents groups in rings A and B of the synthetized chalcone analogues and its antifungal and cytotoxic activity.

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 μM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage.

Nicotine, the main pharmacologically active component in tobacco and cigarette, has some toxic effects and also high potential for addiction. In this study, the effect of artichoke (Cynara scolymus L.) and zeolite nano-materials on urinary excretion of nicotine and consequently elimination of systematically absorbed nicotine was investigated. A simple, valid and highly sensitive high performance liquid chromatography method has been developed for determination of nicotine in rat urine according to guidelines for bioanalysis.It was found that nano-zeolites can cause increase in urinary concentration of nicotine due to its high surface adsorption. Artichoke leaf extract can cause increase in urinary excretion of nicotine in longer post administration times. It was observed that co-administration of nanozeolites and the leaf extract has the synergetic effect on increasing the urinary excretion of nicotine.

The symptomatic treatment of pain associated with spasm of gastrointestinal or genitourinary origin can include the use of spasmolytic agents and/or non-steroidal anti-inflammatory drugs. However, the evidence of a superior effectiveness of combination in comparison with individual drugs is scarce and controversial. A double-blind, randomised, clinical trial study was designed to characterize the analgesic effect and safety of ketorolac and hyoscine butylbromide against hyoscine butylbromide alone in patients with ambulatory acute cramping pain of gastrointestinal and genitourinary origin. 160 patients with a pain level ≥4 in a 1-10 cm visual analogue scale were allocated to receive a fixed dose of ketorolac/hyoscine butylbromide (10 mg/20 mg) or hyoscine butylbromide (20 mg) alone at 6 h intervals, during a 48 h period. Both treatments were similarly effective when compared as a whole or when groups were classified by pain origin. Conversely, when treatments were grouped by pain intensity, ketorolac/hyoscine butylbromide combination showed a significant better pain relief profile than hyoscine butylbromide alone in pain intensity ≥7, but not <7. Data indicate that the oral ketorolac/hyoscine butylbromide mixture could be a better option than hyoscine butylbromide alone in the treatment of some acute intense cramping painful conditions.

The coordination properties of Pt(II) with 5-amino-1,3,4-thiadiazole-2-thiol [CAS 2349-67-9] (L 1 ) and its novel violurate adduct (L 2 ), both in solution and in solid state, are studied by means of conventional IR-spectroscopy, single crystal X-ray diffraction and thermal methods. The complex compounds of L 1 and L 2 , with general formulas [Pt(C2H2N3S2)2] and [Pt(C6H4N6S2O3)(Cl)]Cl respectively, are obtained. Quantum chemical calculations of the ligands are performed with a view to obtain electronic structure and optical properties of the ligands L 1 and L 2 , respectively. The cell viability of the ligands and metal complexes on a panel of human tumor cell lines is evaluated.

In the present study pharmacokinetics and bioequivalence of 2 brands of ciprofloxacin 500 mg were evaluated in 24 healthy male volunteers after a single dose oral administration in an open, randomized, 2-way crossover study.Blood samples were taken before and within 12 h after the administration of the drug. Plasma concentrations of ciprofloxacin were determined by a simple HPLC method with ultraviolet detection. The used method was validated for specificity, accuracy, precision and sensitivity. The mobile phase consisted of 0.025 M phosphoric acid, acetonitrile, and triethylamine. Analytical column was 5 μm Eurosphere C8 with a Eurosphere C8 guard column. The detector wavelength was set at 278 nm and the retention time was 10 min. The pharmacokinetic parameters, including peak plasma concentrations and time needed to reach the peak were obtained directly from plasma concentration-time profiles. The area under the curve was calculated using non-compartmental methods.The Cmax of 1476.8±319.9 ng/mL and 1 423.0±278.4 ng/mL were attained in about 1.67 and 1.58 h for test and reference formulations, respectively. The mean±SD values for AUC0-∞ were 9 665.3±2 880.2 and 9 716.1±2 572.1 ng.hr/mL for test and reference formulations, respectively. The pharmacokinetics parameters AUC0-t, AUC0-∞ and Cmax were calculated for bioequivalence after log-transformation of data. The 90% confidence intervals of test/reference for AUC0-t, AUC0-∞ and Cmax were (95.6-109.9%), (91.8-106.3%) and (95.2-112.8%), respectively and all were within the bioequivalence acceptance range of 80-125%.These results indicate that 2 tested formulations are bioequivalent and thus could be prescribed interchangeably.

A simple HPLC with fluorescence detection method was developed for determination and pharmacokinetic study of Etoposide in dog plasma.Plasma sample pretreatment involved liquid-liquid extraction of 500 µL plasma. The chromatographic separation was carried out on a Gemini C18 column with a mixture of methanol (A) and water (B) (0~5 min, volume of A was 45-50%, 5~10 min, volume of A was 50-90%) used as mobile phase at a flow rate of 0.4 ml/min.These results indicated that the accuracy and precision of the current assay were within the recommendations for assay validation as stipulated in "Guidance for Industry: Bioanalytical Method Validation". Etoposide nanoparticles and injection pharmacokinetic parameters were as follows: T1/2, 2.26 (0.71) and 1.74 (0.43) h;Cmax, 13.24 (5.32) and 8.12 (3.61) µg/ml; AUC0-t, 41.32 (7.33) and 16.53 (4.12) µg · ml - 1 · h; AUC0-∞, 49.54 (9.62) and 19.64 (8.22) µg · ml - 1 · h; MRT, 3.13 (0.54) and 2.06 (0.33) h and CL 7.35 (1.53) and 12.61 (2.22), respectively.This method was fully validated and successfully applied to a preclinical pharmacokinetic study of Etoposide in dogs after i. v. drip administration.