Pub Date : 2011-02-22DOI: 10.3109/10601333.2010.539614
M. Iqbal, K. Al-rashood
A selective, suitable and reproducible HPLC-UV method was developed and validated for the determination and pharmacokinetic investigation of valsartan in human plasma. Valsartan and internal standard (IS), irbesartan, were extracted from plasma samples using liquid–liquid extraction with ethyl acetate + n-hexane (80:20). Chromatographic separation was performed on a Lichrosphere C18 RP Select B column (250 × 4.0 mm i.d; 5 µm particle size) using 20-mM potassium dihydrogen orthophosphate buffer (pH adjusted to 2.7 ± 0.05 using 50% orthophosphoric acid):acetonitrile (60:40 v/v) as the mobile phase at flow rate of 1.2 ml/min. The effluent was monitored using ultraviolet (UV) detection set at 225 nm, having column oven temperature 40°C and sample cooler temperature 8°C ± 0.2°C. The calibration curve was linear over the range of 217.7–6118.4 ng/mL. The intra- and inter-day precisions were within 8.6% and 7.4%, respectively, whereas accuracies were 101.0–107.9% and 103.4–109.5%, respectively. The validated method was successfully applied for the evaluation of pharmacokinetic and bioequivalence parameters of valsartan after oral administration of 160 mg tablets in 18 healthy volunteers.
{"title":"Development and full validation of a quantitative assay for the determination of valsartan in human plasma and its application for bioequivalence study","authors":"M. Iqbal, K. Al-rashood","doi":"10.3109/10601333.2010.539614","DOIUrl":"https://doi.org/10.3109/10601333.2010.539614","url":null,"abstract":"A selective, suitable and reproducible HPLC-UV method was developed and validated for the determination and pharmacokinetic investigation of valsartan in human plasma. Valsartan and internal standard (IS), irbesartan, were extracted from plasma samples using liquid–liquid extraction with ethyl acetate + n-hexane (80:20). Chromatographic separation was performed on a Lichrosphere C18 RP Select B column (250 × 4.0 mm i.d; 5 µm particle size) using 20-mM potassium dihydrogen orthophosphate buffer (pH adjusted to 2.7 ± 0.05 using 50% orthophosphoric acid):acetonitrile (60:40 v/v) as the mobile phase at flow rate of 1.2 ml/min. The effluent was monitored using ultraviolet (UV) detection set at 225 nm, having column oven temperature 40°C and sample cooler temperature 8°C ± 0.2°C. The calibration curve was linear over the range of 217.7–6118.4 ng/mL. The intra- and inter-day precisions were within 8.6% and 7.4%, respectively, whereas accuracies were 101.0–107.9% and 103.4–109.5%, respectively. The validated method was successfully applied for the evaluation of pharmacokinetic and bioequivalence parameters of valsartan after oral administration of 160 mg tablets in 18 healthy volunteers.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"43 1","pages":"13 - 7"},"PeriodicalIF":0.0,"publicationDate":"2011-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77905058","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}
Pub Date : 2011-02-22DOI: 10.3109/10601333.2010.546799
M. Tomar, A. Patni, S. Iyer, A. Khuroo, Sudershan Kumar, N. Thudi, Rakesh K. Jain, Sachin Rana, T. Monif
Randomized, two-way crossover, bioequivalence studies were conducted separately in healthy Mexican and Asian Indian volunteers. One tablet either of test or of reference product was administered after 10 h of overnight fasting. After dosing, serial blood samples were collected for a period of 72 h and 168 h, respectively, for both the studies. Plasma samples were analyzed for citalopram by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0–t, AUC0–72, AUC0–∞, Cmax, and Tmax were determined from plasma concentration-time profiles for both the test and reference formulation of citalopram 20 mg tablets, and were compared statistically to evaluate bioequivalence between the two brands of citalopram. In both the studies, the analysis of variance (ANOVA) did not show any significant difference between the test and reference formulations and 90% confidence intervals (CI) were lying within the acceptable range for bioequivalence. The test and reference formulations exhibited comparable pharmacokinetics profiles and were bioequivalent, but high values of both Cmax (~ 23%) and AUC (~ 34%) were observed in Asian Indian healthy volunteers as compared to the Mexican volunteers. This may be due to the poor metabolism of Citalopram in the Asian population. This difference in the results of pharmacokinetic parameters of Asian Indian and Mexican volunteers may be attributed to ethnic factors.
{"title":"Comparison of pharmacokinetics of citalopram in healthy Asian Indian and Mexican volunteers","authors":"M. Tomar, A. Patni, S. Iyer, A. Khuroo, Sudershan Kumar, N. Thudi, Rakesh K. Jain, Sachin Rana, T. Monif","doi":"10.3109/10601333.2010.546799","DOIUrl":"https://doi.org/10.3109/10601333.2010.546799","url":null,"abstract":"Randomized, two-way crossover, bioequivalence studies were conducted separately in healthy Mexican and Asian Indian volunteers. One tablet either of test or of reference product was administered after 10 h of overnight fasting. After dosing, serial blood samples were collected for a period of 72 h and 168 h, respectively, for both the studies. Plasma samples were analyzed for citalopram by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0–t, AUC0–72, AUC0–∞, Cmax, and Tmax were determined from plasma concentration-time profiles for both the test and reference formulation of citalopram 20 mg tablets, and were compared statistically to evaluate bioequivalence between the two brands of citalopram. In both the studies, the analysis of variance (ANOVA) did not show any significant difference between the test and reference formulations and 90% confidence intervals (CI) were lying within the acceptable range for bioequivalence. The test and reference formulations exhibited comparable pharmacokinetics profiles and were bioequivalent, but high values of both Cmax (~ 23%) and AUC (~ 34%) were observed in Asian Indian healthy volunteers as compared to the Mexican volunteers. This may be due to the poor metabolism of Citalopram in the Asian population. This difference in the results of pharmacokinetic parameters of Asian Indian and Mexican volunteers may be attributed to ethnic factors.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"41 1","pages":"22 - 26"},"PeriodicalIF":0.0,"publicationDate":"2011-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87170133","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}
Pub Date : 2011-02-22DOI: 10.3109/10601333.2010.539230
Jinping Wang, Jianlong Wu, Junfen Yang, Yi Zhuang, Jialin Chen, W. Qian, Jie Tian, Xiaoyan Chen, Dingping She, Fei Peng
The objective of this study was to assess the effects of pharmaceutical care interventions on blood pressure (BP) and medication adherence of patients with primary hypertension in China. A total of 60 patients with primary hypertension were enrolled in the trial for a 12-month period. Participants were randomized to either control group or intervention group in a 1:1 ratio. During the follow-up period, patients in the control group were given regular medi-care, while patients in the intervention group accepted pharmaceutical care. The dates of baseline demographics, medication lists, measurement of medication adherence, and BP values were collected. Statistical analyses were conducted using t-test or χ2 test. After 12 months follow-up, 24-h BP was significantly decreased by 9.75 mmHg (7.1%) for systolic blood pressure (SBP) and 5.88 mmHg (6.6%) for diastolic blood pressure (DBP) in the intervention group (p < 0.05) compared with their initial visit, while there was no significant change in the control group (p > 0.05). The intervention group demonstrated a higher percentage of patients with high adherence (72.41%) at 12 months, whereas the control group hardly had changes in medication compliance. In conclusion, the results indicate that pharmaceutical care intervention might contribute to better BP control of primary hypertension, and could enhance medication compliance of patients.
{"title":"Effects of pharmaceutical care interventions on blood pressure and medication adherence of patients with primary hypertension in China","authors":"Jinping Wang, Jianlong Wu, Junfen Yang, Yi Zhuang, Jialin Chen, W. Qian, Jie Tian, Xiaoyan Chen, Dingping She, Fei Peng","doi":"10.3109/10601333.2010.539230","DOIUrl":"https://doi.org/10.3109/10601333.2010.539230","url":null,"abstract":"The objective of this study was to assess the effects of pharmaceutical care interventions on blood pressure (BP) and medication adherence of patients with primary hypertension in China. A total of 60 patients with primary hypertension were enrolled in the trial for a 12-month period. Participants were randomized to either control group or intervention group in a 1:1 ratio. During the follow-up period, patients in the control group were given regular medi-care, while patients in the intervention group accepted pharmaceutical care. The dates of baseline demographics, medication lists, measurement of medication adherence, and BP values were collected. Statistical analyses were conducted using t-test or χ2 test. After 12 months follow-up, 24-h BP was significantly decreased by 9.75 mmHg (7.1%) for systolic blood pressure (SBP) and 5.88 mmHg (6.6%) for diastolic blood pressure (DBP) in the intervention group (p < 0.05) compared with their initial visit, while there was no significant change in the control group (p > 0.05). The intervention group demonstrated a higher percentage of patients with high adherence (72.41%) at 12 months, whereas the control group hardly had changes in medication compliance. In conclusion, the results indicate that pharmaceutical care intervention might contribute to better BP control of primary hypertension, and could enhance medication compliance of patients.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"183 1","pages":"1 - 6"},"PeriodicalIF":0.0,"publicationDate":"2011-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85451099","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}
Pub Date : 2011-02-22DOI: 10.3109/10601333.2010.544315
E. Kerwin, C. Prazma, Laura B Sutton, D. Stempel
This 52 week study (ADA109057; ClinicalTrials.gov identifier: NCT00452348) was designed to assess the safety and efficacy of fluticasone propionate (FP)/salmeterol 250/50 mcg via DISKUS (FSC) vs FP 250 mcg in subjects with persistent asthma symptomatic on FP 100 mcg. The objective was to demonstrate superiority in lung function (FEV1) of FSC 250/50 mcg vs FP 250 mcg. Secondary objectives included AM PEF, percentage of symptom-free days, and rate of asthma attacks. Three hundred and ten subjects received FSC 250/50 mcg and 318 subjects received FP 250 mcg, both administered twice daily following a 14–21 days of open-label FP 100 mcg. Treatment with FSC 250/50 mcg resulted in an improvement in lung function vs FP 250 mcg (p = 0.09). Additionally, treatment with FSC 250/50 mcg improved AM PEF and increased the percentage of symptom-free days. The asthma attack rate was similar between treatments, as was the safety profile. FSC 250/50 mcg demonstrated improvements in lung function and asthma control vs FP 250 mcg, although statistically significant differences were not consistent. The differences may be representative of this population with less severe disease at entry. In patients with mild-to-moderate persistent asthma FSC offers improved parameters of asthma control compared with ICS alone.
{"title":"Safety and efficacy of long-term treatment with fluticasone propionate and salmeterol via DISKUS versus fluticasone propionate alone","authors":"E. Kerwin, C. Prazma, Laura B Sutton, D. Stempel","doi":"10.3109/10601333.2010.544315","DOIUrl":"https://doi.org/10.3109/10601333.2010.544315","url":null,"abstract":"This 52 week study (ADA109057; ClinicalTrials.gov identifier: NCT00452348) was designed to assess the safety and efficacy of fluticasone propionate (FP)/salmeterol 250/50 mcg via DISKUS (FSC) vs FP 250 mcg in subjects with persistent asthma symptomatic on FP 100 mcg. The objective was to demonstrate superiority in lung function (FEV1) of FSC 250/50 mcg vs FP 250 mcg. Secondary objectives included AM PEF, percentage of symptom-free days, and rate of asthma attacks. Three hundred and ten subjects received FSC 250/50 mcg and 318 subjects received FP 250 mcg, both administered twice daily following a 14–21 days of open-label FP 100 mcg. Treatment with FSC 250/50 mcg resulted in an improvement in lung function vs FP 250 mcg (p = 0.09). Additionally, treatment with FSC 250/50 mcg improved AM PEF and increased the percentage of symptom-free days. The asthma attack rate was similar between treatments, as was the safety profile. FSC 250/50 mcg demonstrated improvements in lung function and asthma control vs FP 250 mcg, although statistically significant differences were not consistent. The differences may be representative of this population with less severe disease at entry. In patients with mild-to-moderate persistent asthma FSC offers improved parameters of asthma control compared with ICS alone.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"55 1","pages":"14 - 21"},"PeriodicalIF":0.0,"publicationDate":"2011-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75362350","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}
Pub Date : 2010-12-01DOI: 10.3109/10601333.2010.513387
Pawan Deep Singh, Lalit Dutta, Onkar Singh, Sanjeev Mishra, A. Khuroo, T. Monif, A. Ahmed, Nirmala Yadav
A simple, sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for quantitation of guaifenesin in human plasma using guaifenesin-d3 as internal standard (IS). Following solid phase extraction, the analyte was chromatographed using an isocratic mobile phase on a reversed-phase C18 column and analyzed by MS in multiple reaction-monitoring (MRM) mode (positive ion mode). The limit of quantitation for this method was 8 ng/mL and the linear dynamic range was 8–2200 ng/mL.
{"title":"Selective, sensitive, and rapid liquid chromatography-tandem mass spectrometry method for determination of Guaifenesin in human plasma","authors":"Pawan Deep Singh, Lalit Dutta, Onkar Singh, Sanjeev Mishra, A. Khuroo, T. Monif, A. Ahmed, Nirmala Yadav","doi":"10.3109/10601333.2010.513387","DOIUrl":"https://doi.org/10.3109/10601333.2010.513387","url":null,"abstract":"A simple, sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for quantitation of guaifenesin in human plasma using guaifenesin-d3 as internal standard (IS). Following solid phase extraction, the analyte was chromatographed using an isocratic mobile phase on a reversed-phase C18 column and analyzed by MS in multiple reaction-monitoring (MRM) mode (positive ion mode). The limit of quantitation for this method was 8 ng/mL and the linear dynamic range was 8–2200 ng/mL.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"52 1","pages":"121 - 127"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75487466","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}
Pub Date : 2010-10-22DOI: 10.3109/10601333.2010.513388
A. Patni, T. Monif, A. Khuroo, S. Iyer, A. Tiwary
The objective of the study was to evaluate the effect of time of administration of food post-dosing on the oral bioavailability of two formulations of itraconazole 100 mg capsule in 24 healthy adult Indian subjects under fasting conditions. Three different paradigms for time of administrations of food post-dose were selected: 4 h, 5 h, and 6 h. A randomized two-treatment, four-period, three-sequence, single dose bioavailability study was conducted. After dosing, serial blood samples were collected for up to 72 h. Plasma samples were analyzed for Itraconazole (ITZ) and its metabolite Hydroxy Itraconazole (OH-ITZ) by a sensitive and validated simultaneous liquid-chromatographic and mass-spectrometric (LC-MS/MS) method. A comparison of effect of post-dose fasting up to 4 h, 5 h, and 6 h on pharmacokinetic parameters of the two formulations was done, and it was found that pharmacokinetic parameters (Cmax, AUC0–t, AUC0–∞, Tmax) were consistent for both formulations in all the paradigms tested. This result suggests no impact on itraconazole bioavailability is observed based on difference in time of administration of food post-dose.
{"title":"A comparative bioavailability study of two formulations of itraconazole 100 mg capsule in healthy human Indian subjects under fasting conditions","authors":"A. Patni, T. Monif, A. Khuroo, S. Iyer, A. Tiwary","doi":"10.3109/10601333.2010.513388","DOIUrl":"https://doi.org/10.3109/10601333.2010.513388","url":null,"abstract":"The objective of the study was to evaluate the effect of time of administration of food post-dosing on the oral bioavailability of two formulations of itraconazole 100 mg capsule in 24 healthy adult Indian subjects under fasting conditions. Three different paradigms for time of administrations of food post-dose were selected: 4 h, 5 h, and 6 h. A randomized two-treatment, four-period, three-sequence, single dose bioavailability study was conducted. After dosing, serial blood samples were collected for up to 72 h. Plasma samples were analyzed for Itraconazole (ITZ) and its metabolite Hydroxy Itraconazole (OH-ITZ) by a sensitive and validated simultaneous liquid-chromatographic and mass-spectrometric (LC-MS/MS) method. A comparison of effect of post-dose fasting up to 4 h, 5 h, and 6 h on pharmacokinetic parameters of the two formulations was done, and it was found that pharmacokinetic parameters (Cmax, AUC0–t, AUC0–∞, Tmax) were consistent for both formulations in all the paradigms tested. This result suggests no impact on itraconazole bioavailability is observed based on difference in time of administration of food post-dose.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"60 1","pages":"128 - 132"},"PeriodicalIF":0.0,"publicationDate":"2010-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81301157","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}
Pub Date : 2010-10-22DOI: 10.3109/10601333.2011.647033
Lalit Dutta, Syed Imran Ahmad, Sanjeev Mishra, A. Khuroo, T. Monif
An analytical method based on liquid chromatography–tandem mass spectrometry (LC-MS-MS) was developed and validated for the determination of glimepiride in human plasma. Glimepiride and glimepiride-d4 (internal standard) were extracted from the plasma by solid phase extraction and chromatographed on a C18 analytical column using an isocratic mobile phase. Detection was carried out by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The chromatographic separation was obtained within 2 min. Linearity was established from 1.00–500.00 ng/mL with a coefficient of determination (r2) of 0.9981 or greater. The lower limit of quantitation (LOQ) was identifiable and reproducible at 1.00 ng/mL with a precision of 3.8%. The method has shown remarkable reproducibility, with intra- and inter-day precision and accuracy <11.3% and <11.0%, respectively. The method was successfully applied for the quantitation of glimepiride in human plasma to support clinical and pharmacokinetic studies.
{"title":"Selective, sensitive, and rapid liquid chromatography – tandem mass spectrometry method for determination of Glimepiride in human plasma","authors":"Lalit Dutta, Syed Imran Ahmad, Sanjeev Mishra, A. Khuroo, T. Monif","doi":"10.3109/10601333.2011.647033","DOIUrl":"https://doi.org/10.3109/10601333.2011.647033","url":null,"abstract":"An analytical method based on liquid chromatography–tandem mass spectrometry (LC-MS-MS) was developed and validated for the determination of glimepiride in human plasma. Glimepiride and glimepiride-d4 (internal standard) were extracted from the plasma by solid phase extraction and chromatographed on a C18 analytical column using an isocratic mobile phase. Detection was carried out by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The chromatographic separation was obtained within 2 min. Linearity was established from 1.00–500.00 ng/mL with a coefficient of determination (r2) of 0.9981 or greater. The lower limit of quantitation (LOQ) was identifiable and reproducible at 1.00 ng/mL with a precision of 3.8%. The method has shown remarkable reproducibility, with intra- and inter-day precision and accuracy <11.3% and <11.0%, respectively. The method was successfully applied for the quantitation of glimepiride in human plasma to support clinical and pharmacokinetic studies.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"51 1","pages":"15 - 22"},"PeriodicalIF":0.0,"publicationDate":"2010-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84533562","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}
Pub Date : 2010-10-22DOI: 10.3109/10601333.2010.501081
M. H. Aburahma, H. M. El‐laithy, Yassin El-Said Hamza
Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor solubility and extensive hepatic first-pass metabolism. In the present work, self-microemulsifying drug delivery systems (SMEDDS) employing long chain triglycerides (LCT) were successfully developed to increase vinpocetine’s solubility and reduce its hepatic first pass metabolism, thus enhancing its overall oral bioavailability. Maisine™35-1 was chosen as the lipid component in the formulated SMEDDS as it showed the maximal vinpocetine solubility within different LCT tested. Feasibility of obtaining SMEDDS, containing Maisine™35-1, together with Transcutol®HP and either Cremophor®EL or Tween 80, was evaluated using ternary phase diagrams. In vitro release studies performed in phosphate buffer of pH 7.4 illustrated that extent of vinpocetine release from SMEDDS was drastically higher than that obtained from commercial Cavinton® tablets. The industrial usefulness of the developed SMEDDS was evaluated regarding their moisture sorption isotherms when filled into gelatin capsules and stored at different relative humidity. Vinpocetine’s optimal SMEDDS did not induce gross changes in the gastrointestinal mucosa of rats at the investigated dose. Moreover, it significantly improved the relative oral bioavailability of vinpocetine compared to Cavinton® tablets. Accordingly, this study suggests that SMEDDS containing LCT under proper optimization and safety assessment can be effectively utilized for oral bioavailability enhancement of vinpocetine.
{"title":"Oral bioavailability enhancement of vinpocetine using self-microemulsifying drug delivery system containing long chain triglycerides: Preparation and in vitro/in vivo evaluation","authors":"M. H. Aburahma, H. M. El‐laithy, Yassin El-Said Hamza","doi":"10.3109/10601333.2010.501081","DOIUrl":"https://doi.org/10.3109/10601333.2010.501081","url":null,"abstract":"Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor solubility and extensive hepatic first-pass metabolism. In the present work, self-microemulsifying drug delivery systems (SMEDDS) employing long chain triglycerides (LCT) were successfully developed to increase vinpocetine’s solubility and reduce its hepatic first pass metabolism, thus enhancing its overall oral bioavailability. Maisine™35-1 was chosen as the lipid component in the formulated SMEDDS as it showed the maximal vinpocetine solubility within different LCT tested. Feasibility of obtaining SMEDDS, containing Maisine™35-1, together with Transcutol®HP and either Cremophor®EL or Tween 80, was evaluated using ternary phase diagrams. In vitro release studies performed in phosphate buffer of pH 7.4 illustrated that extent of vinpocetine release from SMEDDS was drastically higher than that obtained from commercial Cavinton® tablets. The industrial usefulness of the developed SMEDDS was evaluated regarding their moisture sorption isotherms when filled into gelatin capsules and stored at different relative humidity. Vinpocetine’s optimal SMEDDS did not induce gross changes in the gastrointestinal mucosa of rats at the investigated dose. Moreover, it significantly improved the relative oral bioavailability of vinpocetine compared to Cavinton® tablets. Accordingly, this study suggests that SMEDDS containing LCT under proper optimization and safety assessment can be effectively utilized for oral bioavailability enhancement of vinpocetine.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"2 1","pages":"107 - 97"},"PeriodicalIF":0.0,"publicationDate":"2010-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73641898","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}
Pub Date : 2010-10-22DOI: 10.3109/10601333.2010.507768
E. M. Larsen, J. Grarup, D. Gey, Karoline B. Jensen, Ole Kirk
The European Clinical Trials Directive (CTD) came into force on May 1st 2004. The CTD provides the legal basis for monitoring the safety of clinical trials and covers the requirements for notification of SUSAR. Implementation of the CTD into national legislation in each Member State has resulted in various interpretations of CTD requirements. The objective of this paper is to investigate how the European Member States administer the safety reporting requirements of the CTD and to clarify the requirements for SUSAR notification in the different Member States. Data was collected through publicly available sources and questionnaires sent to the Competent Authorities and Ethics Committees in 30 European countries. The results document that Competent Authorities and Ethics Committees in the different Member States administer the legislation very differently. This has resulted in different requirements for notification of SUSARs in the Member States, as well as different requirements between the Competent Authorities and Ethics Committees in the same Member State. These requirements have not previously been described and the present overview of the legislation and the requirements of SUSAR reporting is of immediate practical use to especially non-commercial sponsors when conducting clinical trials in Europe.
{"title":"Notification of suspected and unexpected serious adverse reactions according to the Clinical Trials Directive—A descriptive analysis of the legislation and the requirements in a European context","authors":"E. M. Larsen, J. Grarup, D. Gey, Karoline B. Jensen, Ole Kirk","doi":"10.3109/10601333.2010.507768","DOIUrl":"https://doi.org/10.3109/10601333.2010.507768","url":null,"abstract":"The European Clinical Trials Directive (CTD) came into force on May 1st 2004. The CTD provides the legal basis for monitoring the safety of clinical trials and covers the requirements for notification of SUSAR. Implementation of the CTD into national legislation in each Member State has resulted in various interpretations of CTD requirements. The objective of this paper is to investigate how the European Member States administer the safety reporting requirements of the CTD and to clarify the requirements for SUSAR notification in the different Member States. Data was collected through publicly available sources and questionnaires sent to the Competent Authorities and Ethics Committees in 30 European countries. The results document that Competent Authorities and Ethics Committees in the different Member States administer the legislation very differently. This has resulted in different requirements for notification of SUSARs in the Member States, as well as different requirements between the Competent Authorities and Ethics Committees in the same Member State. These requirements have not previously been described and the present overview of the legislation and the requirements of SUSAR reporting is of immediate practical use to especially non-commercial sponsors when conducting clinical trials in Europe.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"276 1","pages":"108 - 120"},"PeriodicalIF":0.0,"publicationDate":"2010-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73480941","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}
Pub Date : 2010-08-19DOI: 10.3109/10601333.2010.499912
Jennifer S. Li, P. Qaqundah, S. Weinstein, C. Laforce, A. Ellsworth, H. Ortega, T. Ferro
This study studied the safety of fluticasone propionate/salmeterol combination (FSC) 100/50 HFA (2 inhalations of 50/25 mcg) twice daily, compared with fluticasone propionate (FP) 100 HFA (two inhalations of 50 mcg) twice daily, over a 12-week treatment period in subjects aged 4–11 years with persistent asthma. Of the 350 subjects randomized to receive double-blind treatment, 173 received FSC 100/50 HFA and 177 received FP 100 HFA. The two treatment groups were comparable in adverse events profiles, vital signs, asthma exacerbations, oropharyngeal examinations, clinical laboratory tests and urinary cortisol levels. The use of spacer did not meaningfully modify cortisol levels. The pre-specified analysis of 12-lead electrocardiograms (ECGs) identified abnormalities during screening as well as post-randomization in both study treatments, even though randomized subjects were without pre-existing cardiovascular disorders. An ad hoc analysis of the ECG data found no clinically relevant ECG abnormalities either prior to randomization or after randomization to study treatments. Thus, the ECG findings were false-positives related to details of the pre-specified analysis. This study highlights the importance of methodology when interpreting ECG data in a pediatric clinical trial. Overall, both FSC 100/50 HFA and FP 100 HFA were well-tolerated in children aged 4–11 years with persistent asthma.
{"title":"Fluticasone propionate/salmeterol combination in children with asthma: Key cardiac and overall safety results","authors":"Jennifer S. Li, P. Qaqundah, S. Weinstein, C. Laforce, A. Ellsworth, H. Ortega, T. Ferro","doi":"10.3109/10601333.2010.499912","DOIUrl":"https://doi.org/10.3109/10601333.2010.499912","url":null,"abstract":"This study studied the safety of fluticasone propionate/salmeterol combination (FSC) 100/50 HFA (2 inhalations of 50/25 mcg) twice daily, compared with fluticasone propionate (FP) 100 HFA (two inhalations of 50 mcg) twice daily, over a 12-week treatment period in subjects aged 4–11 years with persistent asthma. Of the 350 subjects randomized to receive double-blind treatment, 173 received FSC 100/50 HFA and 177 received FP 100 HFA. The two treatment groups were comparable in adverse events profiles, vital signs, asthma exacerbations, oropharyngeal examinations, clinical laboratory tests and urinary cortisol levels. The use of spacer did not meaningfully modify cortisol levels. The pre-specified analysis of 12-lead electrocardiograms (ECGs) identified abnormalities during screening as well as post-randomization in both study treatments, even though randomized subjects were without pre-existing cardiovascular disorders. An ad hoc analysis of the ECG data found no clinically relevant ECG abnormalities either prior to randomization or after randomization to study treatments. Thus, the ECG findings were false-positives related to details of the pre-specified analysis. This study highlights the importance of methodology when interpreting ECG data in a pediatric clinical trial. Overall, both FSC 100/50 HFA and FP 100 HFA were well-tolerated in children aged 4–11 years with persistent asthma.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"37 1","pages":"87 - 95"},"PeriodicalIF":0.0,"publicationDate":"2010-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75882779","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}
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