Pub Date : 2010-02-26DOI: 10.3109/10601331003604762
H. Gangadharappa, M. Rahamath-Ulla, T. M. Pramod-Kumar, F. Shakeel
The main purpose of this investigation was to develop a controlled release floating drug delivery system (tablet) of verapamil hydrochloride. Floating tablets of verapamil hydrochloride were engineering to extend gastric residence time and hence to enhance its bioavailability. The floating matrix tablets were prepared by direct compression technique using a combination of hydroxyl propyl methyl cellulose (HPMC) and karaya gum as polymers and sodium bicarbonate as generating agent. The prepared floating tablets were evaluated for weight variation test, hardness, thickness, swelling index, in vitro floating capabilities, floating lag time, compatibility studies, and in vitro drug release. This swellable hydrophilic natural karaya gum was used to control the release of drug. The results showed that the optimized formulation F8 containing 23.3% of karaya gum (70 mg) and 13.3% of HPMC (40 mg) had good floating capability, shorter floating lag time, and sustained drug release for the period of 8 h.
{"title":"Floating drug delivery system of verapamil hydrochloride using karaya gum and HPMC","authors":"H. Gangadharappa, M. Rahamath-Ulla, T. M. Pramod-Kumar, F. Shakeel","doi":"10.3109/10601331003604762","DOIUrl":"https://doi.org/10.3109/10601331003604762","url":null,"abstract":"The main purpose of this investigation was to develop a controlled release floating drug delivery system (tablet) of verapamil hydrochloride. Floating tablets of verapamil hydrochloride were engineering to extend gastric residence time and hence to enhance its bioavailability. The floating matrix tablets were prepared by direct compression technique using a combination of hydroxyl propyl methyl cellulose (HPMC) and karaya gum as polymers and sodium bicarbonate as generating agent. The prepared floating tablets were evaluated for weight variation test, hardness, thickness, swelling index, in vitro floating capabilities, floating lag time, compatibility studies, and in vitro drug release. This swellable hydrophilic natural karaya gum was used to control the release of drug. The results showed that the optimized formulation F8 containing 23.3% of karaya gum (70 mg) and 13.3% of HPMC (40 mg) had good floating capability, shorter floating lag time, and sustained drug release for the period of 8 h.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"28 1","pages":"13 - 20"},"PeriodicalIF":0.0,"publicationDate":"2010-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89364604","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 : 2010-02-26DOI: 10.3109/10601330903490462
K. Kaushik, V. Sripuram, S. Bedada, N. Reddy, G. Priyadarshini, K. Devarakonda
Cisplatin is an anti-tumor agent widely employed in cancer chemotherapy. A specific and selective method for the quantitative determination of cisplatin in human plasma and its applications to pharmacokinetic investigations is described. One simple ethanol-induced protein precipitation step followed by simple liquid–liquid extraction with chloroform is the only requirement as sample treatment. The resulting solution is injected into a Wakosil II (5 μm, 250 cm × 4.6 mm I.D.) analytical column. The mobile phase consisted of methanol:water:acetonitrile (40:30:30 v/v/v). The limit of quantitation was 1 μg/mL. The method showed good recovery (93.95%) and within batch recovery was 91.59–97.00%. At all levels intra- and inter-assay precision was lower than 7 and 10%, respectively. The intra- and inter-assay accuracy ranged from −2.7 to 2% and from −3.1 to 4.0%, respectively. The selectivity (discrimination between the parent drug and platinum containing species such as cisplatin metabolites), simplicity and speed of this assay for free cisplatin quantitation should facilitate pharmacokinetic investigations and therapeutic drug monitoring.
顺铂是一种广泛应用于肿瘤化疗的抗肿瘤药物。本文描述了一种用于人血浆中顺铂定量测定的特异性和选择性方法及其在药代动力学研究中的应用。样品处理只需要一个简单的乙醇诱导蛋白质沉淀步骤，然后用氯仿进行简单的液-液萃取。将所得溶液注入Wakosil II (5 μm, 250 cm × 4.6 mm id)分析柱中。流动相为甲醇:水:乙腈(40:30:30 v/v/v)。定量限为1 μg/mL。该方法回收率为93.95%，批内回收率为91.59 ~ 97.00%。在所有水平上，测定内和测定间的精密度分别低于7%和10%。测定内和测定间的准确度分别为- 2.7 ~ 2%和- 3.1 ~ 4.0%。这种游离顺铂定量分析方法的选择性(区分母体药物和含铂物质，如顺铂代谢物)、简单性和速度将有助于药代动力学研究和治疗药物监测。
{"title":"A simple and sensitive validated HPLC method for quantitative determination of cisplatin in human plasma","authors":"K. Kaushik, V. Sripuram, S. Bedada, N. Reddy, G. Priyadarshini, K. Devarakonda","doi":"10.3109/10601330903490462","DOIUrl":"https://doi.org/10.3109/10601330903490462","url":null,"abstract":"Cisplatin is an anti-tumor agent widely employed in cancer chemotherapy. A specific and selective method for the quantitative determination of cisplatin in human plasma and its applications to pharmacokinetic investigations is described. One simple ethanol-induced protein precipitation step followed by simple liquid–liquid extraction with chloroform is the only requirement as sample treatment. The resulting solution is injected into a Wakosil II (5 μm, 250 cm × 4.6 mm I.D.) analytical column. The mobile phase consisted of methanol:water:acetonitrile (40:30:30 v/v/v). The limit of quantitation was 1 μg/mL. The method showed good recovery (93.95%) and within batch recovery was 91.59–97.00%. At all levels intra- and inter-assay precision was lower than 7 and 10%, respectively. The intra- and inter-assay accuracy ranged from −2.7 to 2% and from −3.1 to 4.0%, respectively. The selectivity (discrimination between the parent drug and platinum containing species such as cisplatin metabolites), simplicity and speed of this assay for free cisplatin quantitation should facilitate pharmacokinetic investigations and therapeutic drug monitoring.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"3 1","pages":"1 - 6"},"PeriodicalIF":0.0,"publicationDate":"2010-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73315701","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 : 2009-11-05DOI: 10.3109/10601330903271263
D. Goswami, S. Gurule, A. Khuroo, T. Monif
Losartan and in-vivo active metabolite losartan carboxylic acid (LCA) formation into systemic circulation have been poorly characterized in different races. A bioequivalence study was therefore conducted on healthy male Indian volunteers with 50 mg losartan formulation and unique comparative analysis with other population is presented. Non-compartmental pharmacokinetic analysis elucidated metabolite formation ratio (MR) for losartan: LCA [Cmax = 1.30 and AUC = 0.32] of 50 mg losartan was more varying compared to innovator [Cmax = 0.82 and AUC = 0.22] though bioequivalence requirements were met successfully. This variation was less for losartan 100 mg losartan- hydrochlorothiazide formulation in our previous published bioequivalence study.
{"title":"Bioequivalence model for evaluation of Losartan in human plasma with special reference to drug–metabolite ratio","authors":"D. Goswami, S. Gurule, A. Khuroo, T. Monif","doi":"10.3109/10601330903271263","DOIUrl":"https://doi.org/10.3109/10601330903271263","url":null,"abstract":"Losartan and in-vivo active metabolite losartan carboxylic acid (LCA) formation into systemic circulation have been poorly characterized in different races. A bioequivalence study was therefore conducted on healthy male Indian volunteers with 50 mg losartan formulation and unique comparative analysis with other population is presented. Non-compartmental pharmacokinetic analysis elucidated metabolite formation ratio (MR) for losartan: LCA [Cmax = 1.30 and AUC = 0.32] of 50 mg losartan was more varying compared to innovator [Cmax = 0.82 and AUC = 0.22] though bioequivalence requirements were met successfully. This variation was less for losartan 100 mg losartan- hydrochlorothiazide formulation in our previous published bioequivalence study.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"62 1","pages":"101 - 112"},"PeriodicalIF":0.0,"publicationDate":"2009-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88310924","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 : 2009-11-05DOI: 10.3109/10601330903252198
S. Gurule, T. Monif, P. Verma, A. Khuroo
The objective of this cross-over bioavailability study on clarithromycin was to compare the bioavailability under fasting and five different diets, in 18 healthy adult male human volunteers using validated LC-MS/MS method. A single dose of clarithromycin 500 mg extended release tablet was administered at six occasions: after overnight fasting, after two vegetarian diets (high fat and low fat), two non-vegetarian diets (high fat and low fat), and low fat vegetarian rice. Serial blood samples were collected up to 36 h after dose. A statistically significant food effect was observed for all diets when compared to fasting treatment.
{"title":"Comparison of effect of fasting and of five different diets on the bioavailability of single oral dose of clarithromycin 500 mg extended release tablet","authors":"S. Gurule, T. Monif, P. Verma, A. Khuroo","doi":"10.3109/10601330903252198","DOIUrl":"https://doi.org/10.3109/10601330903252198","url":null,"abstract":"The objective of this cross-over bioavailability study on clarithromycin was to compare the bioavailability under fasting and five different diets, in 18 healthy adult male human volunteers using validated LC-MS/MS method. A single dose of clarithromycin 500 mg extended release tablet was administered at six occasions: after overnight fasting, after two vegetarian diets (high fat and low fat), two non-vegetarian diets (high fat and low fat), and low fat vegetarian rice. Serial blood samples were collected up to 36 h after dose. A statistically significant food effect was observed for all diets when compared to fasting treatment.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"15 1","pages":"73 - 83"},"PeriodicalIF":0.0,"publicationDate":"2009-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73119159","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 : 2009-11-05DOI: 10.3109/10601330903252214
Vijay Kumar, Harish K. Kaushik, Satish B. Kumar, N. Reddy, Narasimha Y. Reddy, T. Kumaraswamy, Praneet Kumar, K. Devarakonda
The population pharmacokinetics of doxorubicin were evaluated based on a mixed-effect model using the NONMEM (VI) program. Doxorubicin in plasma was measured using high-performance liquid chromatography. Plasma concentration measurements (85 plasma samples) of doxorubicin from 28 patients with cancer receiving doxorubicin (with other co-medication) ranging from 20–120 mg by infusion over 1–2 h were analyzed according to a two-compartment model both in FO and FOCE methods. Additive proportional error model was used to describe inter-individual and residual variability. The influence of covariates such as age, body surface area, gender, and clinical laboratory values (SGOT, SGPT) on total body clearance (CL) and volume of distribution (Vd) were examined. No covariate was found to affect the CL and Vd of unchanged doxorubicin. The CL and Vd estimated by FO method were 1.42 L/h and 51.1 L, respectively, and FOCE method are 1.43 L/h and 51.4 L, respectively. The inter-individual variability for CL and Vd and residual variability were 45.8%, 36%, and 12.6%, respectively. The population means and inter-individual and residual variability of pharmacokinetics of doxorubicin were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic approach could be useful to manage doxorubicin cardio toxicity using sparse data in a clinical setting.
{"title":"Population pharmacokinetics of doxorubicin in Indian cancer patients using NONMEM","authors":"Vijay Kumar, Harish K. Kaushik, Satish B. Kumar, N. Reddy, Narasimha Y. Reddy, T. Kumaraswamy, Praneet Kumar, K. Devarakonda","doi":"10.3109/10601330903252214","DOIUrl":"https://doi.org/10.3109/10601330903252214","url":null,"abstract":"The population pharmacokinetics of doxorubicin were evaluated based on a mixed-effect model using the NONMEM (VI) program. Doxorubicin in plasma was measured using high-performance liquid chromatography. Plasma concentration measurements (85 plasma samples) of doxorubicin from 28 patients with cancer receiving doxorubicin (with other co-medication) ranging from 20–120 mg by infusion over 1–2 h were analyzed according to a two-compartment model both in FO and FOCE methods. Additive proportional error model was used to describe inter-individual and residual variability. The influence of covariates such as age, body surface area, gender, and clinical laboratory values (SGOT, SGPT) on total body clearance (CL) and volume of distribution (Vd) were examined. No covariate was found to affect the CL and Vd of unchanged doxorubicin. The CL and Vd estimated by FO method were 1.42 L/h and 51.1 L, respectively, and FOCE method are 1.43 L/h and 51.4 L, respectively. The inter-individual variability for CL and Vd and residual variability were 45.8%, 36%, and 12.6%, respectively. The population means and inter-individual and residual variability of pharmacokinetics of doxorubicin were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic approach could be useful to manage doxorubicin cardio toxicity using sparse data in a clinical setting.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"13 1","pages":"100 - 93"},"PeriodicalIF":0.0,"publicationDate":"2009-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82282396","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 : 2009-11-05DOI: 10.3109/10601330903252206
Harish K. Kaushik, Vijay Kumar, Satish B. Kumar, N. Reddy, V. K. Raghavaiah, K. Devarakonda
The aim of this study was to describe population pharmacokinetics of cisplatin in an Indian cancer population. Dosage adjustment based on individual pharmacokinetic parameters is of considerable importance for effective and safe use of drugs. Extensive work on cisplatin and other was carried out in different cancer patient populations, but no data are available in Indian cancer patients. In the present study 154 steady state concentrations of cisplatin were analyzed from 46 patients. Pharmacostatistical work was done by using NONMEM. The covariates evaluated in this study were age, body weight, height, sex, and creatinine clearance. The model found to best describe the data following the FO and FOCE method was: Clearance (CL) = θ1*(CLCR/74.92) *EXP (η1) and Volume (V) = {θ2 *(AGE/52.3) + θ3*(BSA/1.55)}*EXP (η2). The final model estimates of CL and V estimated by FO method were 3.02 L/h and 2.72 L, respectively, and by FOCE method were 3.39 L/h and 4.48 L, respectively. These parameters are utilized for individualizing the loading and maintenance doses in pediatric patients.
{"title":"Population pharmacokinetics of cisplatin in Asian Indian cancer patients","authors":"Harish K. Kaushik, Vijay Kumar, Satish B. Kumar, N. Reddy, V. K. Raghavaiah, K. Devarakonda","doi":"10.3109/10601330903252206","DOIUrl":"https://doi.org/10.3109/10601330903252206","url":null,"abstract":"The aim of this study was to describe population pharmacokinetics of cisplatin in an Indian cancer population. Dosage adjustment based on individual pharmacokinetic parameters is of considerable importance for effective and safe use of drugs. Extensive work on cisplatin and other was carried out in different cancer patient populations, but no data are available in Indian cancer patients. In the present study 154 steady state concentrations of cisplatin were analyzed from 46 patients. Pharmacostatistical work was done by using NONMEM. The covariates evaluated in this study were age, body weight, height, sex, and creatinine clearance. The model found to best describe the data following the FO and FOCE method was: Clearance (CL) = θ1*(CLCR/74.92) *EXP (η1) and Volume (V) = {θ2 *(AGE/52.3) + θ3*(BSA/1.55)}*EXP (η2). The final model estimates of CL and V estimated by FO method were 3.02 L/h and 2.72 L, respectively, and by FOCE method were 3.39 L/h and 4.48 L, respectively. These parameters are utilized for individualizing the loading and maintenance doses in pediatric patients.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"10 1","pages":"84 - 92"},"PeriodicalIF":0.0,"publicationDate":"2009-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89547033","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 : 2009-08-21DOI: 10.1080/10601330903143942
S. Singh, P. Verma, B. Razdan
The objective of the work was to develop, optimize, and evaluate a self-microemulsifying drug delivery system of the poorly water-soluble drug, carvedilol. Solubility of carvedilol was determined in various vehicles. Ternary and pseudo-ternary phase diagrams were constructed to indentify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. Zeta potential was measured in the absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using PCA and AHCA, a multivariate statistical analysis. Decrease in t50% and increase in DE attributed to small globule size and eventually higher surface area. The relevance of differences in t50% and DE was evaluated statistically by two-way ANOVA. DRIFTS, DSC, and X-RD studies indicated no incompatibility between drug, oil, and surfactants. The results of this study indicate that the SMEDD formulations of carvedilol owing to nanosize have the potential to enhance its absorption, without interaction or incompatibility between the ingredients.
{"title":"Development and characterization of a carvedilol-loaded self-microemulsifying delivery system","authors":"S. Singh, P. Verma, B. Razdan","doi":"10.1080/10601330903143942","DOIUrl":"https://doi.org/10.1080/10601330903143942","url":null,"abstract":"The objective of the work was to develop, optimize, and evaluate a self-microemulsifying drug delivery system of the poorly water-soluble drug, carvedilol. Solubility of carvedilol was determined in various vehicles. Ternary and pseudo-ternary phase diagrams were constructed to indentify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. Zeta potential was measured in the absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using PCA and AHCA, a multivariate statistical analysis. Decrease in t50% and increase in DE attributed to small globule size and eventually higher surface area. The relevance of differences in t50% and DE was evaluated statistically by two-way ANOVA. DRIFTS, DSC, and X-RD studies indicated no incompatibility between drug, oil, and surfactants. The results of this study indicate that the SMEDD formulations of carvedilol owing to nanosize have the potential to enhance its absorption, without interaction or incompatibility between the ingredients.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"28 1","pages":"50 - 64"},"PeriodicalIF":0.0,"publicationDate":"2009-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82198287","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 : 2009-08-21DOI: 10.1080/10601330903200692
T. Eid, Patrick DiTullio, Sachin A. Shah
{"title":"Does linezolid-induced tongue discoloration need further investigation?","authors":"T. Eid, Patrick DiTullio, Sachin A. Shah","doi":"10.1080/10601330903200692","DOIUrl":"https://doi.org/10.1080/10601330903200692","url":null,"abstract":"","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"25 1","pages":"37 - 38"},"PeriodicalIF":0.0,"publicationDate":"2009-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73087969","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 : 2009-08-21DOI: 10.1080/10601330903012436
Dilip Devineni, Simon A Paulos, Ruhi V. Ubale, B. Rayaprolu, R. Palaniappan
Pneumonia is a deadly respiratory disease inflicting millions of people in third world countries. Current vaccination strategies which include polysaccharide-based vaccines are not effective against all strains of pneumonia. Furthermore, these vaccines are given through parenteral route instead of the more preferred mucosal route which has the obvious advantage of eliciting both systemic as well as mucosal immune responses. This review intends to understand the etiology, treatment options, and potential delivery systems for the vaccination against pneumonia via mucosal route. Various vaccination options including current polysaccharide-based vaccinations along with potential protein-based vaccines have been discussed.
{"title":"Approaches and issues towards development of efficient mucosal vaccines against pneumonia","authors":"Dilip Devineni, Simon A Paulos, Ruhi V. Ubale, B. Rayaprolu, R. Palaniappan","doi":"10.1080/10601330903012436","DOIUrl":"https://doi.org/10.1080/10601330903012436","url":null,"abstract":"Pneumonia is a deadly respiratory disease inflicting millions of people in third world countries. Current vaccination strategies which include polysaccharide-based vaccines are not effective against all strains of pneumonia. Furthermore, these vaccines are given through parenteral route instead of the more preferred mucosal route which has the obvious advantage of eliciting both systemic as well as mucosal immune responses. This review intends to understand the etiology, treatment options, and potential delivery systems for the vaccination against pneumonia via mucosal route. Various vaccination options including current polysaccharide-based vaccinations along with potential protein-based vaccines have been discussed.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"4 1","pages":"39 - 49"},"PeriodicalIF":0.0,"publicationDate":"2009-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87488720","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 : 2009-06-01DOI: 10.1080/10601330902919797
D. Goswami, Ajay Kumar, A. Khuroo, T. Monif, S. Gurule, N. Thudi, V. Shrivastav, S. Dubey
A sensitive high throughput LC/MS/MS method fully validated as per USFDA guidelines is described for pharmacokinetic estimation of flecainide in human plasma using loperamide as the internal standard. Plasma samples were monitored by cation exchange solid phase extraction achieving 78.6% extraction efficiency (mean recovery) followed by chromatographic separation on a PurospherStar RP-18e column. Detection was carried out on an API positive ESI by MRM transitions m/z 415.2/301.1 and 477.3/266.3 for flecainide and loperamide respectively. High sensitivity of 1.17ng/ml, dynamic linearity of 1.17–396.75 ng/ml and short run time within 3 minutes are other interesting aspects of this new bioanalytical method. This method was successfully applied to a pharmacokinetic study with 100mg tablet flecainide administered in Indian population for the first time. A randomized, single dose, two sequence, cross over study design was used to evaluate bioequivalence on 40 healthy male fasted volunteers and blood samples were collected up to 96 hours post dose. Noncompartmental pharmacokinetic analysis was used to evaluate AUC0-t, AUC0-inf, Cmax, Tmax, T1/2 and λz scaled on a 90% confidence interval approach. Average bioequivalence results showed ratios of least square means and its 90% CIs for ln-transformed Cmax, AUC0-t and AUC0-inf for flecainide were 99.99 (95.21–104.99) %, 98.27(93.89–102.86)% and 98.08(93.68–102.68)% respectively. Both the test and reference products were closely comparable in terms of rate and extent to which the drugs access the systemic circulation.
{"title":"Liquid chromatographic tandem mass spectrometric validated method for pharmacokinetic estimation of flecainide in human plasma","authors":"D. Goswami, Ajay Kumar, A. Khuroo, T. Monif, S. Gurule, N. Thudi, V. Shrivastav, S. Dubey","doi":"10.1080/10601330902919797","DOIUrl":"https://doi.org/10.1080/10601330902919797","url":null,"abstract":"A sensitive high throughput LC/MS/MS method fully validated as per USFDA guidelines is described for pharmacokinetic estimation of flecainide in human plasma using loperamide as the internal standard. Plasma samples were monitored by cation exchange solid phase extraction achieving 78.6% extraction efficiency (mean recovery) followed by chromatographic separation on a PurospherStar RP-18e column. Detection was carried out on an API positive ESI by MRM transitions m/z 415.2/301.1 and 477.3/266.3 for flecainide and loperamide respectively. High sensitivity of 1.17ng/ml, dynamic linearity of 1.17–396.75 ng/ml and short run time within 3 minutes are other interesting aspects of this new bioanalytical method. This method was successfully applied to a pharmacokinetic study with 100mg tablet flecainide administered in Indian population for the first time. A randomized, single dose, two sequence, cross over study design was used to evaluate bioequivalence on 40 healthy male fasted volunteers and blood samples were collected up to 96 hours post dose. Noncompartmental pharmacokinetic analysis was used to evaluate AUC0-t, AUC0-inf, Cmax, Tmax, T1/2 and λz scaled on a 90% confidence interval approach. Average bioequivalence results showed ratios of least square means and its 90% CIs for ln-transformed Cmax, AUC0-t and AUC0-inf for flecainide were 99.99 (95.21–104.99) %, 98.27(93.89–102.86)% and 98.08(93.68–102.68)% respectively. Both the test and reference products were closely comparable in terms of rate and extent to which the drugs access the systemic circulation.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"29 1","pages":"24 - 36"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83501229","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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