AAPS PharmSci最新文献

A national survey of U.S. pharmacists in 2000: Assessing nonresponse bias of a survey methodology 2000年美国药剂师全国调查:评估调查方法的无反应偏差

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps030433

D. Mott, Craig A. Pederson, W. Doucette, C. Gaither, J. Schommer

{"title":"A national survey of U.S. pharmacists in 2000: Assessing nonresponse bias of a survey methodology","authors":"D. Mott, Craig A. Pederson, W. Doucette, C. Gaither, J. Schommer","doi":"10.1208/ps030433","DOIUrl":"https://doi.org/10.1208/ps030433","url":null,"abstract":"The first objective of this study was to assess the existence of nonresponse bias to a national survey of licensed pharmacists conducted in 2000. Three methods were used to assess nonresponse bias. The second objective of the study was to examine reasons why sampled licensed pharmacists did not respond to the national survey of licensed pharmacists. We used data from 2204 respondents to a national survey of pharmacists and from 521 respondents to a survey of nonrespondents to the national survey. We made comparisons between respondents for 5 variables: employment status, gender, age, highest academic degree, and year of initial licensure. Chi-square tests were used to examine differences in the 5 variables between respondents to the first mailing and second mailing of the survey, early and late respondents to the survey, and respondents to the survey and respondents to the nonrespondent survey. There were no significant differences between first mailing and second mailing respondents, but there were differences in each variable except year of licensure between early and late respondents. These differences likely were due to regional bias possibly related to differences in mailing times. There were differences between respondents and nonrespondents in terms of employment status and year of licensure. The main reasons for not responding to the survey were that it was too long or that it was too intrusive. Overall, the survey methodology resulted in a valid sample of licensed pharmacists. Nonresponse bias should be assessed by surveying nonrespondents. Future surveys of pharmacists should consider the length of the survey and the address where it is sent.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"29 1","pages":"76-86"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81979811","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}

引用次数: 25

Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method 化学发光法评价不同黄酮类化合物的抗氧化活性

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps050220

S. Georgetti, R. Casagrande, V. D. Mambro, A. Azzolini, M. Fonseca

{"title":"Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method","authors":"S. Georgetti, R. Casagrande, V. D. Mambro, A. Azzolini, M. Fonseca","doi":"10.1208/ps050220","DOIUrl":"https://doi.org/10.1208/ps050220","url":null,"abstract":"The objective of the present investigation was to study the antioxidant action of different flavonoids (quercetin, glabridin, red clover, and Isoflavin Beta, an isoflavones mixture) in order to determine if they could be added to a topical formulation used to treat damage caused by free radicals. Samples of 10 μL of the test compounds at different concentrations were mixed with 0.1 M phosphate buffer, pH 7.4, and a luminol solution was added to yield a final concentration of 0.113 mM. Hydrogen peroxide was then added at a final concentration of 0.05 mM. The reaction was started by introducing the horse-radish peroxidase enzyme at a final concentration of 0.2 IU/mL, in a final volume of 1.0 mL. Chemiluminescence was measured for 10 minutes at room temperature, and dimethylsulfoxide (DMSO) was used as a control. All samples showed marked inhibition of oxidative stress, with a concentration-dependent action for quercetin and Isoflavin Beta. The highest inhibition was observed with glabridin and the dry red clover extract. All flavonoids proved to be adequate for addition to topical formulations because of their high antioxidant activity.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"51 1","pages":"111-115"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90823685","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}

引用次数: 79

The composite solubility versus pH profile and its role in intestinal absorption prediction 复合溶解度与pH值的关系及其在肠道吸收预测中的作用

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps050104

B. Hendriksen, M. Félix, M. Bolger

{"title":"The composite solubility versus pH profile and its role in intestinal absorption prediction","authors":"B. Hendriksen, M. Félix, M. Bolger","doi":"10.1208/ps050104","DOIUrl":"https://doi.org/10.1208/ps050104","url":null,"abstract":"The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the advanced compartmental absorption and transit model. Absorption simulations were carried out for virtual monobasic drugs having a range of pKa, log D, and dose values as a function of presumed solubility and permeability. Results were normally expressed as the combination that resulted in 25% absorption. Absorption of basic drugs was found to be a function of the whole solubility/pH relationship rather than a single solubility value at pH 7. In addition, the parameter spaces of greatest sensitivity were identified. We compared 3 theoretical scenarios: the GIT pH range overlapping (1) only the salt solubility curve, (2) the salt and base solubility curves, or (3) only the base curve. Experimental solubilities of 32 compounds were determined at pHs of 2.2 and 7.4, and they nearly all fitted into 2 of the postulated scenarios. Typically, base solubilities can be simulated in silico, but salt solubilities at low pH can only be measured. We concluded that quality absorption simulations of candidate drugs in most cases require experimental solubility determination at 2 pHs, to permit calculation of the whole solubility/pH profile.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"25 1","pages":"35-49"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73829399","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}

引用次数: 71

Assuring quality and performance of sustained and controlled release parenterals: Workshop report 确保持续控释注射剂的质量和性能:车间报告

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040205

D. Burgess, A. Hussain, T. Ingallinera, Mei-ling Chen

引用次数: 89

Influence of fluoxetine on olanzapine pharmacokinetics 氟西汀对奥氮平药代动力学的影响

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040209

D. Gossen, J. D. Suray, F. Vandenhende, C. Onkelinx, D. Gangji

{"title":"Influence of fluoxetine on olanzapine pharmacokinetics","authors":"D. Gossen, J. D. Suray, F. Vandenhende, C. Onkelinx, D. Gangji","doi":"10.1208/ps040209","DOIUrl":"https://doi.org/10.1208/ps040209","url":null,"abstract":"Conventional antidepressant treatment fails for up to 30% of patients with major depression. When there are concomitant psychotic symptoms, response rates are even worse. Thus, subsequent treatment often includes combinations of antidepressants or augmentation with antipsychotic agents. Atypical antipsychotic agents such as olanzapine cause fewer extrapyramidal adverse effects than conventional antipsychotics; for that reason, they are an advantageous augmentation strategy for treatment-resistant and psychotic depression. The purpose of this study was to assess the potential for pharmacokinetic interaction between olanzapine and fluoxetine, a popular antidepressant that is a selective serotonin reuptake inhibitor. The pharmacokinetics of 3 identical single therapeutic doses of olanzapine (5 mg) were determined in 15 healthy nonsmoking volunteers. The first dose of olanzapine was taken alone, the second given after a single oral dose of fluoxetine (60 mg), and the third given after 8 days of treatment with fluoxetine 60 mg, qd. Olanzapine mean C max was slightly higher (by about 18%) and mean CL/F was slightly lower (by about 15%) when olanzapine was coadministered with fluoxetine in single or multiple doses. Olanzapine mean t 1/2 and median t max did not change. Although the pharmacokinetic effects of fluoxetine on olanzapine were statistically significant, the effects were small and are unlikely to modify olanzapines safety profile. The mechanism of influence is consistent with an inhibition of CYP2D6, which is known to control a minor pathway of olanzapine metabolism.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"4 1","pages":"56-61"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84626155","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}

引用次数: 39

Skin oxygenation after topical application of liposome-entrapped benzyl nicotinate as measured by EPR oximetry in vivo: Influence of composition and size 局部应用脂质体包裹的烟酸苄后，用EPR血氧仪在体内测量皮肤氧合:成分和大小的影响

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps050102

J. Kristl, Zrinka Abramovié, Marjeta Šentjure

{"title":"Skin oxygenation after topical application of liposome-entrapped benzyl nicotinate as measured by EPR oximetry in vivo: Influence of composition and size","authors":"J. Kristl, Zrinka Abramovié, Marjeta Šentjure","doi":"10.1208/ps050102","DOIUrl":"https://doi.org/10.1208/ps050102","url":null,"abstract":"New and improved drug delivery systems are the important subject of much scientific research. The development of formulations that increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with healing processes affected by the level of oxygen. We have use EPR oximetry in vivo to compare the influence of liposomal formulations of different size and composition with that of hydrogel with respect to the action of the entrapped benzyl nicotinate (BN). Following the topical application of BN onto the skin of mice, pO2 increase was measured by low-frequency EPR as a function of time. The effect of BN was evaluated by 3 different parameters: lag-time, time needed for maximum pO2 increase, and overall effectiveness expressed by the area under the response-time curve. An increase in skin oxygenation was observed after BN application. The results show that the effect of BN incorporated in liposomes is achieved more rapidly than the effect from hydrophilic gel. The composition of the liposomes significantly affects the time at which BN starts to act and, to a lesser extent, the maximum increase of pO2 in skin and the effectiveness of BN action. However, the size of the liposomes influences both the effectiveness of BN action and the time at which BN starts to act. After repeated application of liposomes, the pO2 baseline increased and the response of the skin tissue was faster. Our results demonstrate that EPR oximetry is a useful method for evaluating oxygen changes after drug application and for following the time course of their action.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"326 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80382516","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}

引用次数: 21

cDNA Microarray analysis of vascular gene expression after nitric oxide donor infusion in rats: Implications for nitrate tolerance mechanisms 一氧化氮供体输注后大鼠血管基因表达的cDNA芯片分析:硝酸盐耐受机制的意义

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040208

E. Wang, W. Lee, D. Brazeau, H. Fung

{"title":"cDNA Microarray analysis of vascular gene expression after nitric oxide donor infusion in rats: Implications for nitrate tolerance mechanisms","authors":"E. Wang, W. Lee, D. Brazeau, H. Fung","doi":"10.1208/ps040208","DOIUrl":"https://doi.org/10.1208/ps040208","url":null,"abstract":"Vascular nitrate tolerance is often accompanied by changes in the activity and/or expression of a number of proteins. However, it is not known whether these changes are associated with the vasodilatory properties of nitrates, or with their tolerance mechanisms. We examined the hemodynamic effects and vascular gene expressions of 2 nitric oxide (NO) donors: nitroglycerin (NTG) and S-nitroso-N-acetylpenicillamine (SNAP). Rats received 10 μg/min NTG, SNAP, or vehicle infusion for 8 hours. Hemodynamic tolerance was monitored by the maximal mean arterial pressure (MAP) response to a 30-μg NTG or SNAP bolus challenge dose (CD) at various times during infusion. Gene expression in rat aorta after NTG or SNAP treatment was determined using cDNA microarrays, and the relative differences in expression after drug treatment were evaluated using several statistical techniques. MAP response of the NTG CD was attenuated from the first hour of NTG infusion (P<.001, analysis of variance [ANOVA]), but not after SNAP (P>.05, ANOVA) or control infusion (P> .05, ANOVA). Student t-statistics revealed that 447 rat genes in the aorta were significantly altered by NTG treatment (P <.05). An adjusted t-statistic approach using resampling techniques identified a subset of 290 genes that remained significantly different between NTG treatment vs control. In contrast, SNAP treatment resulted in the up-regulation of only 7 genes and the downregulation of 34 genes. These results indicate that continuous NTG infusion induced widespread changes in vascular gene expression, many of which are consistent with the multifactorial and complex mechanisms reported for nitrate tolerance.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"45 1","pages":"45-55"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74010131","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}

引用次数: 21

Evaluation of USP apparatus 3 for dissolution testing of immediate-release products 速释产品溶出度试验用USP仪器3的评价

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040101

Lawrence X. Yu, Jin T. Wang, A. Hussain

{"title":"Evaluation of USP apparatus 3 for dissolution testing of immediate-release products","authors":"Lawrence X. Yu, Jin T. Wang, A. Hussain","doi":"10.1208/ps040101","DOIUrl":"https://doi.org/10.1208/ps040101","url":null,"abstract":"We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly soluble drugs, acyclovir and furosemide, were chosen as model drugs. The dissolution profiles of both innovator and generic IR products were determined using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute (dpm). The dissolution profiles from USP apparatus 3 were compared to those from USP apparatus 2 using the f 2 similarity test. The dissolution profile from USP apparatus 3 generally depends on the agitation rate, with a faster agitation rate producing a faster dissolution rate. It was found that USP apparatus 3 at the extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2 or distinguish dissolution characteristics for the IR products of metoprolol, ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide tablets using USP apparatus 3. Although it is primarily designed for the release testing of extended-release products, USP apparatus 3 may be used for the dissolution testing of IR products of highly soluble drugs, such as metoprolol and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir. USP apparatus 3 offers the advantages of avoiding cone formation and mimicking the changes in physiochemical conditions and mechanical forces experienced by products in the gastrointestinal tract.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"26 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90080267","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}

引用次数: 67

Allometric scaling of xenobiotic clearance: Uncertainty versus universality 异种生物清除的异速缩放:不确定性与普遍性

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps030429

T. Hu, W. Hayton

{"title":"Allometric scaling of xenobiotic clearance: Uncertainty versus universality","authors":"T. Hu, W. Hayton","doi":"10.1208/ps030429","DOIUrl":"https://doi.org/10.1208/ps030429","url":null,"abstract":"Statistical analysis and Monte Carlo simulation were used to characterize uncertainty in the allometric exponent (b) of xenobiotic clearance (CL). CL values for 115 xenobiotics were from published studies in which at least 3 species were used for the purpose of interspecies comparison of pharmacokinetics. The b value for each xenobiotic was calculated along with its confidence interval (CI). For 24 xenobiotics (21%), there was no correlation between log CL and log body weight. For the other 91 cases, the mean±standard deviation of the b values was 0.74±0.16; range: 0.29 to 1.2. Most (81%) of these individual b values did not differ from either 0.67 or 0.75 at P=0.05. When CL values for the subset of 91 substances were normalized to a common body weight coefficient (a), the b value for the 460 adjusted CL values was 0.74; the 99% CI was 0.71 to 0.76, which excluded 0.67. Monte Carlo simulation indicated that the wide range of observed b values could have resulted from random variability in CL values determined in a limited number of species, even though the underlying b value was 0.75. From the normalized CL values, 4 xenobiotic subgroups were examined: those that were (i) protein, and those that were (ii) eliminated mainly by renal excretion, (iii) by metabolism, or (iv) by renal excretion and metabolism combined. All subgroups except (ii) showed a b value not different from 0.75. The b value for the renal excretion subgroup (21 xenobiotics, 105 CL values) was 0.65, which differed from 0.75 but not from 0.67.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"2 1","pages":"30-43"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78673525","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}

引用次数: 89

Novel system to investigate the effects of inhaled volume and rates of rise in simulated inspiratory air flow on fine particle output from a dry powder inhaler 研究吸入量和模拟吸入气流上升速率对干粉吸入器细颗粒输出的影响的新系统

AAPS PharmSci Pub Date : 2008-01-01 DOI: 10.1208/ps040211

V. Chavan, R. Dalby

{"title":"Novel system to investigate the effects of inhaled volume and rates of rise in simulated inspiratory air flow on fine particle output from a dry powder inhaler","authors":"V. Chavan, R. Dalby","doi":"10.1208/ps040211","DOIUrl":"https://doi.org/10.1208/ps040211","url":null,"abstract":"This study evaluated the effect of inhaled volume and simulated inspiratory flow rate ramps on fine particle output from dry powder inhalers (DPIs). A simple, robust system was developed to account for “rate of rise” (ramp) effects while maintaining a constant air flow through a multi-stage liquid impinger (MSLI), used for sizing the emitted particles. Ramps were programmed to reach 30 and 60 L/min over 100 milliseconds; 500 milliseconds; and 1, 2, and 3 seconds. Rotahaler was chosen as the test DPI. Testing was done with simulated inhalation volumes of 2 L and 4 L. Testing was also carried out using the USP apparatus 4. At 30 L/min, for a 2 L volume, the amount of drug exiting the device in fine particle fraction (FPF) increased from 2.33 μg to 6.04 μg from the 3-second ramp to the 100-millisecond ramp, with 11.64 μg in FPF for the USP (no ramp) method. At the same flow rate, for a 4 L volume, FPF increased from 2.23 μg to 8.45 μg, with 10.25 μg for the USP method. At 60 L/min, similar trends were observed. In general, at both flow rates, an increase in FPF was noted going from the shallowest to the steepest ramp. However, there were no significant differences in FPF when a 2 L inhaled volume was compared with a 4 L volume at each flow rate. Overall, these data suggest that the existing USP apparatus may overestimate FPF at flow rates lower than those recommended by the USP.","PeriodicalId":6918,"journal":{"name":"AAPS PharmSci","volume":"3 1","pages":"7-12"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78667675","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}

引用次数: 27