Methods and findings in experimental and clinical pharmacology最新文献

Aclidinium bromide, AE-37, Alemtuzumab, AMA1-C1/ISA 720, Amlodipine besylate/atorvastatin calcium, Arachidonic acid, Arbaclofen placarbil, Aripiprazole, ARQ-621, Azelnidipine, Azilsartan medoxomil potassium; Bevacizumab, Biphasic insulin aspart, Bortezomib; Choriogonadotropin alfa, CTS-1027; Dapagliflozin, Dasatinib, Deforolimus, Degarelix acetate, Denufosol tetrasodium, Desvenlafaxine succinate, Dronedarone hydrochloride, Duloxetine hydrochloride, Dutasteride; Enfuvirtide, Entecavir, Etaracizumab, Everolimus, Exenatide, Ezetimibe; Ferric carboxymaltose, Fludarabine, Foretinib; Gefitinib, GFT-505, GSK-256066; HPV-6/11/16/18, HuM195/rGel, HyperAcute-Lung cancer vaccine; I5NP, Imatinib mesylate, Imexon, Insulin detemir, Insulin glargine, Ivabradine hydrochloride; L2G7, Lacosamide, Lapatinib ditosylate, Lenalidomide, Lidocaine/prilocaine, Liposomal vincristine, Liraglutide, Lixivaptan; Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, Methoxy polyethylene glycol-epoetin-β, Mirabegron, Morphine/oxycodone, MR Vaccine, MSC-1936369B, Mycophenolic acid sodium salt; Narlaprevir, N-Desmethylclozapine; Ocriplasmin, Olaparib, Olmesartan medoxomil, Olmesartan medoxomil/azelnidipine, ONO-5334, ONO-8539; Palifermin, Panitumumab, Pardoprunox hydrochloride, PCV7, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pexelizumab, PF-337210, Pitavastatin calcium; Raltegravir potassium, Recombinant interleukin-7, Regadenoson, Reniale, Roflumilast, Rosuvastatin calcium; Safinamide mesilate, SB-1518, SCH-527123, Selumetinib, Sipuleucel-T, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talaporfin sodium, Tanespimycin, Technosphere/Insulin, Telaprevir, Telatinib, Telcagepant, Telmisartan/hydrochlorothiazide, Teriparatide, Testosterone transdermal gel, TH-302, Tiotropium bromide, Tocilizumab, Trabedersen, Tremelimumab; Valsartan/amlodipine besylate, Vernakalant hydrochloride, Visilizumab, Voreloxin, Vorinostat.

This cross-sectional, observational study evaluated the use of levetiracetam oral solution in usual clinical practice. Patients ≥ 16 years with partial-onset seizures (had received levetiracetam oral solution for ≥ 28 days) completed a study questionnaire assessing overall acceptability of levetiracetam oral solution, specific organoleptic characteristics (taste, taste intensity, aftertaste), ease of use and convenience. Tolerability was assessed by evaluating adverse events. Of 389 patients, 92.8% (361/389) were evaluable for acceptability, all (389) for tolerability; 65.3% (236/361) rated levetiracetam oral solution very acceptable or acceptable, 41.5% (150/361) pleasant or very pleasant, 54.3% (196/361) neither strong nor mild taste intensity and indicated the drug left an aftertaste (most stated aftertaste did not bother them), 75.3% very easy or easy to use and 61.8% very convenient or convenient to use. There was a positive relationship between overall acceptability of levetiracetam oral solution and favorable responses for organoleptic characteristics, ease of use, convenience and patients' evaluation of treatment compliance (P < 0.0001 for each). Of the 176/353 who previously received another antiepileptic drug and reported preference for a medication, 72.2% (127/176) preferred levetiracetam oral solution and 39/389 (10%) reported adverse events. Levetiracetam oral solution demonstrated a high degree of patient acceptability in adult patients with partial-onset seizures and was well tolerated.

A specific, sensitive and simple method was developed to determine the levels of both atorvastatin and ortho-hydroxy atorvastatin in human plasma. The analytes and internal standard pitavastatin were extracted from plasma by liquid-liquid extraction, separated on a Zorbax SB-C18 column, eluted with a mobile phase of water:acetonitrile (45:55 v/v), both containing 5% methanol and 0.01% formic acid. Detection was performed with an electrospray ionization triple quadrupole mass spectrometer in positive ion mode using multiple reaction monitoring. The standard calibration curves of atorvastatin and ortho-hydroxy atorvastatin were linear in the concentration range of 0.2-20 and 0.1-20 ng/mL, respectively. The intra- and inter-day precisions were < 7.7% and the accuracy was within ± 5.9%. The method has been successfully used for the study of the pharmacokinetics of atorvastatin and ortho-hydroxy atorvastatin in Chinese patients with coronary heart disease after a single oral dose of 20 mg atorvastatin. The mean values for the area under the plasma concentration-time curve for atorvastatin and ortho-hydroxy atorvastatin were 63.1 and 46.9 ng.h/mL, respectively.

A-3309, Abobotulinumtoxin A, Adalimumab, AIDSVAX gp120 B/E, ALVAC E120TMG, Atorvastatin calcium; Bepridil, Bevacizumab; Candesartan cilexetil, Capecitabine, Cetuximab, Clopidogrel; Dapagliflozin, Dasatinib, Denosumab, Dexmedetomidine hydrochloride, Diacetylmorphine, Diannexin, Docetaxel, Dutasteride; Entecavir, Eplerenone, Erlotinib hydrochloride, Escitalopram oxalate, Everolimus, Ezetimibe; Fesoterodine fumarate, Flagellin.HuM2e, Fluzone; Glimepiride/rosiglitazone maleate; Hyaluronic acid-paclitaxel bioconjugate; IDX-184, Imatinib mesylate, Infliximab, Insulin glargine, Irbesartan; JX-594; Landiolol, Latrunculin B, Levocetirizine dihydrochloride, Liraglutide, Lyprinol; Metformin, Metronidazole/tetracycline hydrochloride/bismuth biskalcitrate, Mipomersen sodium, Mycophenolic acid sodium salt; Nalfurafine hydrochloride, Nilotinib hydrochloride monohydrate; Paclitaxel nanoparticles, Paclitaxel poliglumex, Peginterferon alfa-2a, Peginterferon alfa-2b, Perospirone hydrochloride, Pimavanserin tartrate, Pirfenidone, Pitavastatin calcium, Prasterone, Prasugrel, Pregabalin, Ranelic acid distrontium salt, Ranibizumab, Remimazolam, Risedronate, Rosuvastatin calcium; Silodosin, Silybin phosphatidylcholine complex, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sorafenib, Sunitinib malate; Tadalafil, Tamsulosin hydrochloride, Technosphere/insulin, Telmisartan, Temsirolimus, Teriparatide, Thymalfasin, Ticagrelor, Toltedorine-XR, Tramadol-XR, Triphosadenine, Trospium-XR; Val8-GLP-1(7-37)OH, Valsartan, Vardenafil hydrochloride hydrate, Varenicline tartrate, Velaglucerase alfa; Zoledronic acid monohydrate.

A major inhibitory neurotransmitter of the nervous system, GABA (gamma-aminobutyric acid), is involved in mammalian thermoregulation. The present study investigated the influence of GABAergic neurotransmission-enhancing drugs, in a model of morphine-induced hyperthermia in conscious rats. We used body temperature assays to examine the effects of GABA-acting drugs on morphine-induced hyperthermia. In rats, low doses of morphine injected i.p. produced significant hyperthermia in a body temperature assay that was significantly attenuated upon pretreatment with GABA-acting drugs. These results suggest the existence of opioidergic-GABAergic interactions in a complex process of thermoregulation.

The nuclear factor-kappaB (NF-κB) in cardiac vascular endothelial cells (type II VEC) is a key factor that activates delayed xenograft rejection (DXR), and therefore inhibition of NF-κB gene expression may alleviate post-transplant rejection. siRNA technology was used to inhibit NF-κB p65 gene expression in ICR mice. After jugular vein injection of siRNA/in vivo-jetPEI complex, fluorescence levels of FAM-labeled siRNA in hearts and lungs were much higher after jugular vein injection than tail vein injection, suggesting more efficient siRNA delivery to the heart through the jugular vein. The amount of FAM fluorescence of hearts increased to the highest level between 48 and 72 hours after injection, and decreased gradually 1 week after injection. A minimum dose of 6 nmol NF-κB p65 siRNA and a siRNA/in vivo-jetPEI ratio of 6 (N/P = 6) were required for in vivo siRNA-mediated gene silencing in the heart. Under these conditions, application of siRNA/in vivo-jetPEI complexes from the jugular vein successfully suppressed NF-κB p65 expression in the heart. The same strategy can be applied to heart transplant animal models to protect against NF-κB gene-related type II VEC activation and xenograft rejection.

Schizophrenia is a chronic psychiatric disorder and pharmacotherapy plays a major role in its management. The 1950s and early 1960s saw milestones in the introduction of psychotropic drugs in clinical practice. A review of drug prescriptions in different settings provides an insight into the pattern of drug use, identifies drug-related problems and may be used to compare recommended guidelines with actual practice. This effort led to the evaluation of the drug prescribing pattern of antipsychotics in patients attending the psychiatric clinic at a government hospital. The data from 371 antipsychotic medication prescriptions that included 200 prescriptions for schizophrenia were collected during one month (1rst-31rst August 2008) at the outpatient pharmacy department. The mean age of patients was 35.0 years (SD = 1.131), with a male to female ratio of 2:1. The most widely used oral antipsychotic was haloperidol (16.3%) while the most common depot preparation prescribed was zuclopenthixol decanoate (8.8%). The daily dose of the average antipsychotic prescribed in this clinic was 342.06 mg equivalent of chlorpromazine. There was no relation between the doses received and ethnicity of the patient (Malay, Chinese or Indian). However, there was a significant relationship between the prescribed dose and patient age (P < 0.042). Nearly 32% of the schizophrenia patients were prescribed with atypical antipsychotics such as olanzapine (10.8%), risperidone (10.0%), quetiapine (7.6%) and clozapine (3.2%). Monotherapy was given to 73.0% of the schizophrenia patients. The majority of patients also received antidepressants. To conclude, this study gave evidence that physicians had a strong preference for monotherapy with conventional antipsychotic drugs while the use of atypical drugs was less prevalent.

The pathogenesis of a number of diseases like cardiovascular diseases, cancer and neurological disorders, has been associated with changes in the balance of certain trace elements. In this study we aimed at investigating the levels of trace elements like calcium, copper, iron and zinc, in ischemic stroke patients in comparison with healthy controls. Serum samples were collected from 256 ischemic stroke patients and 180 healthy, age and sex matched controls. Trace element levels were detected using commercially available kits and an Auto-Analyzer (ChemWell 2910, Awareness Technology, US). The concentrations of calcium, copper and iron were not significantly different in patients when compared to healthy controls. The concentration of zinc was significantly lower in stroke patients (P = 0.001) as compared to normal subjects. To conclude, patients with acute ischemic stroke have reduced levels of serum zinc. Zinc may represent an independent risk factor for stroke and therefore a possible target for prevention. Additional studies are needed to further examine the role of zinc in the pathogenesis of stroke.

The ethnomedicinal uses of Musanga cecropioides R. Apud Tedlie (Cecropiaceae) as a hypotensive agent have been scientifically investigated and reported. This work examines its effect on various models of diarrhea based on the ethnomedicinal use of the plant for this indication. The stem bark of the plant, used locally by soaking in gin (alcoholic), was treated with absolute ethanol and the extract screened for antidiarrheal activity using the castor oil-induced diarrhea and small intestinal motility models in mice. Its effects on the isolated rat ileum were also investigated. In the castor oil-induced diarrhea, the extract at 100, 200, and 400 mg/kg significantly (P < 0.05 at all doses) showed dose-related antidiarrheal effects as indicated by reduction in the number and weight of fecal material produced. The extract at all doses used also significantly (P < 0.05, P < 0.0001 and P < 0.0001 at 100, 200, and 400 mg/kg doses, respectively) decreased the intestinal motility of the treated mice as compared to controls and inhibited acetylcholine-induced contractions (P < 0.0001). In the isolated rat ileum the extract at 5 and 10 mg/mL, remarkably inhibited acetylcholine induced contractions, indicating a probable antimuscarinic effect of the extract. The results obtained confirmed that the stem bark of M cecropioides has antidiarrheal activity as used in folkloric medicine.

Endothelial dysfunction is one of the many proposed mechanisms of hypertension and it may justify, at least in part, the increased blood pressure of hypertensive subjects. Nevertheless, the exact mechanisms involved in the hypertensive condition of obese Zucker rats are unclear. In this study, we measured the arterial blood pressure (tail cuff method) of four groups of seven, female, obese Zucker rats each. The rats of groups 1-4 were 9-12, 15-18, 21-24 and 27-30 weeks old respectively. We also evaluated the responses of aortic rings to KCl, methoxamine and acetylcholine, in these animals. Aortic rings were successively exposed to 80 mM KCl and to methoxamine (10(-8)-10(-5) M). The endothelium-dependent relaxation to acetylcholine (10(-9)-10(-5) M) was also established in the methoxamine-precontracted tissue (precontraction close to 80% of the maximum effect of methoxamine). A clear increase in the arterial blood pressure was observed when the age of these animals increased. The contractile responses to KCl and methoxamine were lower in the aortic rings of rats with increased arterial blood pressure. The response to acetylcholine was lower in the rings from 15-18, 21-24 and 27-30 weeks old rats, than in the younger groups. In conclusion, obese Zucker rats develop hypertension and endothelial dysfunction. Nevertheless, the arterial contractions elicited by depolarization or by α(1)-adrenoceptor stimulation decrease in aged, obese Zucker rats.