Arzneimittel-Forschung-Drug Research最新文献

{"title":"Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry.","authors":"H-L Li,&nbsp;J-C He,&nbsp;M Bai,&nbsp;Q-Y Song,&nbsp;E-F Feng,&nbsp;G-X Rao,&nbsp;G-L Xu","doi":"10.1055/s-0031-1298021","DOIUrl":"https://doi.org/10.1055/s-0031-1298021","url":null,"abstract":"<p><p>An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C18 column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH3COO] - →179 and m/z 415 [M + CH3COO] - →179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 3","pages":"138-44"},"PeriodicalIF":0.0,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1298021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30414400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence evaluation of 2 tablet formulations of entecavir in healthy chinese volunteers: a single-dose, randomized-sequence, open-label crossover study.","authors":"J Jin,&nbsp;J Liu,&nbsp;J Chen,&nbsp;L Zhao,&nbsp;Z Ma,&nbsp;X Chen,&nbsp;M Huang,&nbsp;G Zhong","doi":"10.1055/s-0031-1297964","DOIUrl":"https://doi.org/10.1055/s-0031-1297964","url":null,"abstract":"<p><p>A randomized, 2-way crossover study was conducted in healthy Chinese male volunteers to evaluate the bioequivalence of a new generic formulation of entecavir (CAS 142217-69-4) tablets (test) and the available branded formulation (reference) to meet the requirements for marketing the test product in China. Test and reference tablets were administered as a single dose on 2 treatment days separated by a 2-week washout period. Blood samples were collected for a period of 24 h following drug administration. Plasma concentration of entecavir was determined by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Pharmacokinetic parameters were calculated using a noncompartmental model. Bioequivalence was determined by calculating 90% CIs for the ratios of Cmax, AUC0-t and AUC0-∞ values for the test and reference products. Tolerability was assessed by monitoring vital signs, laboratory tests and interviews with the volunteers before administration and every 2 h during the study. The 90% CIs of entecavir for Cmax, AUC0-t and AUC0-∞ were 95.2-106.9%, 98.4-104.6% and 97.3-104.4%, respectively, which fell within the interval of 80-125%. No clinically important adverse effects were reported. These results suggested that the test formulation of entecavir tablets met the regulatory criterion for bioequivalence to the reference formulation.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 3","pages":"113-6"},"PeriodicalIF":0.0,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1297964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30417268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence of a novel minitablet formulation of levetiracetam.","authors":"C de Mey,&nbsp;V Dimitrova,&nbsp;P Lennartz,&nbsp;M Wangemann","doi":"10.1055/s-0031-1297965","DOIUrl":"https://doi.org/10.1055/s-0031-1297965","url":null,"abstract":"<p><p>To investigate whether rapidly dissolving levetiracetam minitablets are bioequivalent to a single tablet of the same strength. 2 bioequivalence studies were carried out investigating the 1 000 mg and 1 500 mg strength of such novel medicinal products relative to single-unit film-coated originator tablets for reference. In each study, 16 young healthy subjects (8 males, 8 females) were investigated according to a 2,2,2-cross-over design with 1 week between periods for washout purposes. Each time, the plasma pharmacokinetics were profiled for 36 h after dosing.There were no relevant differences between the formulations with regard to tmax, apparent terminal half-life and the mean residence time. For the 1 000 mg strength, the estimated ratios of the true treatment means for test to reference were 1.008 (90% CI: 0.897-1.133), 1.010 (90% CI: 0.964-1.057), and 1.012 (90% CI: 0.965-1.062) for Cmax, AUC(0-tz), and AUC(0-∞), respectively; for the 1 500 mg strength, the respective ratio estimates were 0.960 (90% CI: 0.892-1.034), 1.005 (90% CI: 0.971-1.040), and 1.006 (90% CI: 0.970-1.042).Rapidly dissolving levetiracetam minitablets are bioequivalent with the originator single-unit reference tablets. Such alternative medicinal products make it easier and more convenient to individualise treatment of patients with epilepsy eligible to treatment with levetiracetam, particularly at higher doses when single-unit tablets, by being very large are difficult to swallow.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 2","pages":"94-8"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1297965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30468315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative determination of pidotimod in human plasma by liquid chromatography tandem mass spectrometry: application to a bioequivalence study.","authors":"H-G Lou,&nbsp;Z-R Ruan,&nbsp;B Jiang","doi":"10.1055/s-0031-1297983","DOIUrl":"https://doi.org/10.1055/s-0031-1297983","url":null,"abstract":"<p><p>A highly sensitive and simple LC-MS/MS method after one-step protein precipitation was developed and validated for determination of pidotimod (CAS 121808-62-6) in human plasma using dextrophan (CAS 125-73-5) as internal standard (IS). Pidotimod and IS were separated on a YMC-ODS-AQ C18 column using 0.5% formic acid and methanol as a mobile phase at a flow rate of 0.3 mL/min. Detection was performed on positive ion mode of the transitions at 245.0→134.0 for pidotimod and 258.1→157.0 for IS by selected reaction monitoring (SRM). The assay exhibited a linear range of 0.05-10.0 µg/mL. The lower limit of quantification were 0.05 µg/mL. Validation results indicated that the accuracy as determined from quality control samples was in the range of  - 4.00-6.48%. Intra-day and inter-day precision was ≤  8.35% and ≤  8.00%, respectively. The developed method was successfully applied to a bioequivalence study in 20 healthy Chinese volunteers following a single oral dose of 800 mg pidotimod. The simple, inexpensive protein precipitation and high-throughput method makes it a suitable and valuable tool in the investigation of the clinical pharmacokinetics and bioequivalence.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 2","pages":"99-104"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1297983","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30468316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, pharmacodynamics, and tolerability of a generic formulation of exenatide: a randomized, open-label, single- and multiple-dose study in healthy Chinese volunteers.","authors":"S Shi,&nbsp;Y Liu,&nbsp;Z Li,&nbsp;J Wu,&nbsp;X Zhou,&nbsp;F Zeng","doi":"10.1055/s-0031-1295484","DOIUrl":"https://doi.org/10.1055/s-0031-1295484","url":null,"abstract":"<p><p>A randomized, open-label, dose-escalating study was designed to assess the pharmacokinetics, pharmacodynamics and tolerability of single and multiple subcutaneous administrations of exenatide in 24 healthy Chinese volunteers. The effects of gender on the pharmacokinetics of exenatide were also evaluated. Subjects were randomized to receive a single and multiple subcutaneous doses of 5 or 10 μg of exenatide. Following the single dose subjects received exenatide twice daily on days 2-4 and once on day 5. Sequential blood samples were collected at regular intervals from 0 to 8 h after single administration. Concomitantly the serum glucose concentrations were measured in each sample. Tolerability was assessed using physical examination, vital signs, laboratory analysis, and by interview of subjects. Pharmacokinetic parameters for exenatide after subcutaneous administration of a single dose of 5-10 μg were as follows: Cmax=77.7 (13.9) and 136.1 (15.2) pg/mL; AUC0-t=184.2 (49.7) and 309.7 (52.3) pg·h/mL; AUC0-∞=225.8 (77.4) and 365.4 (68.8) pg·h/mL; tmax (median [range])=1.00 (0.75-1.50) and 1.00 (0.75-1.50) h; t1/2 (mean [range])=1.4 (0.7-3.2) and 1.8 (1.0-2.5) h, respectively. Because of its short t1/2, Css, min could not be detected in any plasma samples prior to daily dosing on days 3-5. Pharmacokinetic parameters for exenatide after administration of multiple doses of 5 or 10 μg were as follows: Cmax=81.2 (12.2) and 144.5 (13.3) pg/mL; AUC0-t=181.1 (39.4) and 275.6 (45.0) pg·h/mL; AUC0-∞=217.2 (44.8) and 313.3 (48.4) pg·h/mL; tmax=1.10 (0.75-1.25) and 1.00 (1.00-1.25) h; t1/2=1.6 (0.8-2.2) and 1.4 (0.9-2.7) h, respectively. Both doses of exenatide were associated with significant reductions in serum glucose concentrations (P<0.001) when compared to baseline levels. Mean percentage of maximal decline for serum glucose concentrations after single and multiple doses were 15.6% and 19.9% for 5 μg, respectively; as well as 26.3% and 28.7% for 10 μg, respectively. 12 of the 24 subjects reported a total of 75 adverse events. The rate increased with higher doses of exenatide: after 5 μg only one subject experienced at least 1 adverse event but following 10 μg 11 subjects were affected. 2 subjects receiving the higher dose of 10 μg exenatide dropped out because of adverse events (nausea and vomiting). The most common adverse events were of gastrointestinal origin (e. g. decreased appetite, nausea and vomiting) and of mild severity. In conclusion, in healthy Chinese subjects, AUC and Cmax increased in proportion to the dose, whereas t1/2 was independent of dose. The pharmacokinetic parameters after multiple dosing were consistent with those after single doses. No significant gender differences were noted for pharmacokinetic variables. Both exenatide doses were associated with significant reductions in serum glucose levels. Adverse events were mainly of gastrointestinal origin and their incidence was dose-dependent.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 2","pages":"75-82"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1295484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30467790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of formulation and excipients towards enhanced permeation of curcumin.","authors":"B Wahlang,&nbsp;D Kabra,&nbsp;Y B Pawar,&nbsp;K Tikoo,&nbsp;A K Bansal","doi":"10.1055/s-0031-1295487","DOIUrl":"https://doi.org/10.1055/s-0031-1295487","url":null,"abstract":"<p><p>Curcumin (CRM) (CAS number 458-37-07), a naturally-occurring molecule, has diverse pharmacological actions. Recently our research group demonstrated that poor permeability also contributes to its poor oral bioavailability. A self nano-emulsifying drug delivery system (CRM SNEDDS) consisting of Labrasol, Gelucire 44/14, Vitamin E TPGS and PEG 400 was designed and provided 16 times improvement in oral bioavailability in rats, at a dose of 250 mg/kg body weight. Caco-2 cell transport studies were conducted for CRM SNEDDS and CRM in the presence of individual excipients, to determine the extent of improvement in permeability. Papp values for CRM, CRM SNEDDS and CRM in combination with 4 individual excipients were calculated. Transepithelial electrical resistance value was assessed to evaluate the cell morphology and the cellular tight junctions. Permeation of a transcellular marker, Lucifer Yellow was used as a marker to assess monolayer integrity. The tested excipient concentrations were found to be non-toxic to the cell monolayer in 2 h incubation. Results showed that the Papp increased 6.35 times for curcumin in CRM SNEDDS as compared to CRM. Individual excipients enhanced permeation from 1.97 to 6.35 times, with Labrasol showing the highest enhancement of 6.35 times.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 2","pages":"88-93"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1295487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30468314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The wind of change: respecting the past, embracing the future.","authors":"M Wehling","doi":"10.1055/s-0031-1295486","DOIUrl":"https://doi.org/10.1055/s-0031-1295486","url":null,"abstract":"","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1295486","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30458556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of olanzapine and clozapine on radial maze performance in naive and MK-801-treated mice.","authors":"O Mutlu,&nbsp;I K Celikyurt,&nbsp;G Ulak,&nbsp;P Tanyeri,&nbsp;F Y Akar,&nbsp;F Erden","doi":"10.1055/s-0031-1291360","DOIUrl":"https://doi.org/10.1055/s-0031-1291360","url":null,"abstract":"<p><p>Attention, working memory and long-term memory dysfunctions are the most commonly seen cognitive impairments in schizophrenic patients. Conflicting results exist regarding the effects of antipsychotics on cognitive abnormalities. The aim of this study was to investigate the effects of atypical antipsychotic drugs olanzapine (0.4, 0.8 and 1.25 mg/kg, i.p.) and clozapine (0.5 and 1 mg/kg, i.p.) on spatial working memory in naive and MK-801 (0.2 mg/kg, i.p.) treated BALB-c mice in an 8-arm radial arm maze (RAM) task. None of the antipsychotic drugs studied altered number of errors in naive mice, whereas MK-801 significantly increased working memory errors in RAM test. Olanzapine and clozapine potently reversed MK-801 induced increasement of working memory errors. Olanzapine and clozapine prolonged latency of the animals in naive mice. The MK-801-induced enhancement in the speed of mice in performing the RAM task was blocked by olanzapine but not clozapine. Our study shows that atypical antipsychotics olanzapine and clozapine might improve cognitive deficits in schizophrenic patients.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 1","pages":"4-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1291360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30458559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence and pharmacokinetic comparison of 3 metformin extended/sustained release tablets in healthy Indian male volunteers.","authors":"L S Batolar,&nbsp;M Iqbal,&nbsp;T Monif,&nbsp;A Khuroo,&nbsp;P L Sharma","doi":"10.1055/s-0031-1295428","DOIUrl":"https://doi.org/10.1055/s-0031-1295428","url":null,"abstract":"<p><p>This study was undertaken to compare the bioavailability and pharmacokinetic properties of 3 marketed product of metformin (CAS 1115-70-4) extended/sustained release formulation in Indian male volunteers. Study was designed as an open-label, randomized, 3-treatment, single-dose, crossover, bioavailability study comparing 3 marketed brands of 500 mg metformin extended/sustained release tablets in 18 healthy human male volunteers under fed condition. A single oral dose of 500 mg metformin sustained release products, test A (Glycomet SR), test B (Bigomet SR) and extended release reference product was administered as per computer generated randomization schedule during 3 period of the study having 7 days of washout period. A liquid Chromatography mass spectroscopy method for the determination of metformin in human plasma was developed and validated using metformin-D6 as an internal standard. A noncompartment pharmacokinetic method was employed to determine the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-∞ and t½) of metformin using WinNonlin-Node 4.0 software. Cmax, AUC0-t and AUC0-∞ were used to test for bioequivalence after log transformation of plasma data. The predetermined regulatory range of 90% CI for bioequivalence was 0.80 to 1.25. The 90% confidence intervals for log transformed data for Cmax, AUC0-t and AUC0-∞ for test A vs. reference were 82.11-98.91, 86.29-102.17 and 86.34-102.59 respectively whereas for test B vs. reference were 104.39-125.76, 94.78-112.22 and 92.85-110.33 respectively. The results of this study suggest that the test A was bioequivalent to reference product, whereas test B was not as per regulatory defined criteria.</p>","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 1","pages":"22-6"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1295428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30457374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A special new year.","authors":"W Wiegers,&nbsp;R Wenzel","doi":"10.1055/s-0031-1299715","DOIUrl":"https://doi.org/10.1055/s-0031-1299715","url":null,"abstract":"","PeriodicalId":56084,"journal":{"name":"Arzneimittel-Forschung-Drug Research","volume":"62 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0031-1299715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30458558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}