Arzneimittel-Forschung[JOURNAL]
Sun
200 papers
Bioanalytical method development, validation and quantification of flupirtine maleate in rat plasma by liquid chromatography-tandem mass spectrometry.
Kandasamy K, Gowdra VS, Nammalvar H … +1 more , Govindarajan AK
Arzneimittelforschung · 2011 · PMID 22282956 · Publisher ↗
A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of flupirtine (CAS 75507-68-5) in rat...
A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of flupirtine (CAS 75507-68-5) in rat plasma samples. The chromatographic separation was achieved with a reverse phase column (4.6 x 50 mm, 5 microm) and the mobile phase consisted of cyanomethane and 5 mM ammonium formate buffer pH 4.5 (70:30 v/v) as eluent, at a flow rate of 0.6 mL/min. Labetalol (CAS 36894-69-6) was used as an internal standard. The effluence was ionized by positive electrospray ionization and measured by mass spectrometry. The retention times of flupirtine and labetalol were found to be 2.16 and 1.66 min respectively. The calibration curve was linear (r2 > or = 0.99) ranging from 0.98 to 1000 ng/ml and the lower limit of quantification was 0.98 ng/ mL. Inter-day and Intra-day precision were lower than 5% (CV) and accuracy ranged from 90 to 110% in terms of percent accuracy. Mean extraction recovery was found to be above 86.5%. The method was successfully applied for evaluation of the pharmacokinetic profile of flupirtine in male Sprague-Dawley rats and validated for excellent selectivity, accuracy, precision, recovery and stability.
Effect of Myrtol standardized on mucus hypersecretion and clearance of Pseudomonas aeruginosa in a rat model of chronic obstructive pulmonary disease.
Cao L, Chen Y, Zhao Y … +4 more , Zhang H, Wang S, Wang Z, Kang J
Arzneimittelforschung · 2011 · PMID 22282955 · Publisher ↗
This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divi...
This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divided into 6 groups: control (n = 6), exposure to cigarette smoke (CS, n = 6), CS plus Myrtol standardized treatment (CS + M, n = 6), Pseudomonas aeruginosa (PA) infection (PA, n = 25), CS + PA (n = 25), and CS + PA + M (n = 25). For all 62 CS rats, they were exposed to cigarette smoke for a period of 12 weeks. During this time period the 31 CS + M rats (CS + M; CS + PA + M) received 300 mg/kg/day Myrtol standardized intragastrically always 30 min prior to smoke exposure. For CS + PA and CS + PA + M rats, intratracheal PA inoculation was performed after the 12 weeks of smoke exposure. All intratracheal PA inoculations were followed by a post-infection examination at 6, 12, 24, 48 and 72 h in each 5 rats. All study animals were euthanized and their lungs were excised; the left lung was homogenized for determination of bacterial load and measurements of TNF-alpha and IL-6, the right lungs were preserved for histo- and immunohistochemical examinations (e. g. MUC5AC). The lungs from CS rats were pathologically similar to those of COPD patients with the characteristics of goblet cell metaplasia and MUC5AC hypersecretion. CS animals had a significantly greater number of MUC5AC positive cells in the bronchial epithelial cells, and significantly increased expression levels of TNF-alpha and IL-6 after PA infection. However, the administration of Myrtol standardized significantly (p = 0.002) attenuated MUC5AC hypersecretion, measured as integrity optical density (IOD), in CS + M rats (45.98 +/- 6.25) as compared to CS alone (65.55 +/- 11.18) rats. The same applies at different time points between CS + PA rats (65.15 +/- 11.94, 75.88 +/- 7.42, 81.2 +/- 6.49, 75.14 +/- 6.85 and 67.32 +/- 10.61, respectively) and CS + PA + M rats (47.08 +/- 4.78, 54.22 +/- 6.59, 65.4 +/- 6.12, 59.98 +/- 4.96 and 48.43 +/- 7.29, respectively). Similar effects were found in the production of IL-6 and TNF-alpha in the CS + PA + M lungs. Similarly the bacterial load of 10,980 +/- 4,253 CFU in CS + PA + M was significantly lower compared to 42,400 +/- 3,296 CFU in CS + PA lungs after 72 h PA infection. In conclusion, this experimental study demonstrates a significant therapeutic effect of Myrtol standardized in treating common pathological conditions, such as airway mucus hypersecretion and defect of mucociliary functions in COPD.
Bioequivalence study of two clopidogrel film-coated tablet formulations in healthy volunteers.
Setiawati E, Yunaidi DA, Handayani LR … +3 more , Santoso ID, Setiawati A, Tjandrawinata RR
Arzneimittelforschung · 2011 · PMID 22282954 · Publisher ↗
The present study was performed to compare the bioavailability of two clopidogrel 75 mg film-coated tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period,...
The present study was performed to compare the bioavailability of two clopidogrel 75 mg film-coated tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period, two-sequence cross-over study which included 24 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were assessed based on the concentrations of clopidogrel (CAS 120202-66-6) parent compound. In each of the two study periods (separated by a washout of one week) a single dose of test or reference drug was administered. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 24 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (t(max)), and the elimination half life (t1/2). The geometric mean ratios (90% CI) of the test drug/reference drug for clopidogrel parent compound were 95.19% (81.63-110.90%) for AUCt, 95.55% (80.50-113.42%) for AUCinf, and 100.18% (80.87-124.09%) for Cmax. The 90% confidence intervals calculated for AUCt and Cmax of clopidogrel parent compound were within the standard bioequivalence range (80-125% for AUC and Cmax). It was concluded that the two clopidogrel film-coated tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.
Ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of nitrendipine in dog plasma and its application to a pharmacokinetic study of a solid self-emulsifying pellet formulation.
Liu Y, Wang Z, Sun J … +2 more , Wang Y, He Z
Arzneimittelforschung · 2011 · PMID 22282953 · Publisher ↗
A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of nitrendipine (NTD, CAS 39562-70-4) i...
A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of nitrendipine (NTD, CAS 39562-70-4) in dog plasma. Using propranolol hydrochloride (CAS 318-98-9) as an internal standard (IS), plasma samples pretreatment adopted a simple liquid-liquid extraction process with diethyl ether. Separation was carried out by a gradient elution on an Acquity UPLC BEH C18 column with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile. Detection was performed by a triple-quadrupole mass spectrometry with positive electrospray ionization (ESI) as source ionization in multiple-reaction monitoring (MRM) mode at m/z 361.0 --> 315.0 for NTD and m/z 260.2 --> 116.0 for IS. The method demonstrated good linearity at the concentrations ranged from 0.1-200 ng/mL and the lower limit of quantification (LLOQ) of NTD was 0.1 ng/mL. The intra- and inter-day relative standard deviations (RSD) were less than 10%. The mean extraction recoveries of NTD and IS were 90.2% and 82.4%, respectively. Finally, the method was successfully applied to a pharmacokinetic study of home-made solid self-emulsifying pellets and conventional NTD tablets in beagle dogs following a single oral administration.
Bioequivalence evaluation of 2 tablet formulations of entecavir in healthy chinese volunteers: a single-dose, randomized-sequence, open-label crossover study.
Jin J, Liu J, Chen J … +5 more , Zhao L, Ma Z, Chen X, Huang M, Zhong G
Arzneimittelforschung · 2012 Mar · PMID 22282264 · Publisher ↗
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 for...
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.
Comparative bioequivalence study of leflunomide tablets in Indian healthy volunteers.
Agarwal S, Das A, Ghosh D … +3 more , Sarkar AK, Chattaraj TK, Pal TK
Arzneimittelforschung · 2012 Mar · PMID 22278631 · Publisher ↗
The pharmacokinetics of teriflunomide [CAS No. 163451-81-8], the metabolite of leflunomide [CAS No. 75706-12-6] has been evaluated in adult human volunteers after oral administration of tablet formulation. However, no pu...
The pharmacokinetics of teriflunomide [CAS No. 163451-81-8], the metabolite of leflunomide [CAS No. 75706-12-6] has been evaluated in adult human volunteers after oral administration of tablet formulation. However, no published data is available regarding the bioavailability of this in the Indian population. In light of the above, a study was designed to carry out a bioequivalence study of 2 preparations of leflunomide 20 mg in healthy Indian male volunteers.24 healthy male volunteers (age, 25±4.1 years; weight, 57.58±7.01 kg) were enrolled in this study. Each subject received a test and reference formulation in a single dose, fasting 2 period, 2 way crossover study with a wash out period of 4 weeks. Analysis of teriflunomide from plasma samples was done by a simple and sensitive HPLC method using UV detection developed in our laboratory. An analysis of variance was performed on the pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ using GLM procedures in which sources of variation were subject, formulation, and period.The results indicated that there are no statistically significant differences between the 2 products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters. 90% confidence limits for the log transformed data of Cmax, AUC0-t, AUC0-∞. were within the acceptable range of 0.80-1.25.The results indicate that the 2 products are bioequivalent in terms of rate and extent of drug absorption. Both the preparations were well tolerated with no adverse reactions throughout the study.
Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry.
Li HL, He JC, Bai M … +4 more , Song QY, Feng EF, Rao GX, Xu GL
Arzneimittelforschung · 2012 Mar · PMID 22278630 · Publisher ↗
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 an...
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.
Protective effect of Puerarin on β-amyloid-induced neurotoxicity in rat hippocampal neurons.
Lin F, Xie B, Cai F … +1 more , Wu G
Arzneimittelforschung · 2012 Apr · PMID 22278629 · Publisher ↗
Puerarin (CAS Number 3681-99-0), a major isoflavone glycoside purified from Pueraria lobata, was reported to possess antioxidative and estrogen-like biological activities. Recent studies showed that puerarin protects dif...
Puerarin (CAS Number 3681-99-0), a major isoflavone glycoside purified from Pueraria lobata, was reported to possess antioxidative and estrogen-like biological activities. Recent studies showed that puerarin protects different cell types from damage caused by a variety of toxic stimuli. In the present study, we investigated the neuroprotective effect of puerarin against Aβ25-35-induced neurotoxicity in cultured hippocampal neurons, as well as the underlying mechanism(s). Following exposure of cells to Aβ25-35, cell survival and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were reduced while production of reactive oxygen species (ROS) was increased. Preincubation of the cells with puerarin prior to Aβ25-35 exposure increased cell survival and GSH-Px and CAT activities and decreased ROS production. It was previously shown that overactivation of glycogen synthase kinase-3β (GSK-3β) is implicated in Aβ-induced cell death. In this study, Aβ25-35 treatment is found to increase GSK-3β activity and pretreatment with puerarin preventesAβ-induced activation of GSK-3β based on Western blot analysis. In addition, puerarin is shown to activate protein kinase B (PKB)/Akt, an important upstream kinase of GSK-3β, possibly promoting subsequent GSK-3β inhibition. Our data suggest that puerarin attenuates cell death induced by Aβ25-35 via various mechanisms, which might be beneficial for the treatment of Alzheimer's disease.
Pharmacokinetics and biodistribution of paclitaxel-loaded microspheres.
Yan F, Tang S, Fu Q
Arzneimittelforschung · 2012 Apr · PMID 22270845 · Publisher ↗
Paclitaxel(PTX)-loaded microspheres composed of poly(D,L-lactide-co-glycolide) (PLGA) were prepared by an O/W emulsion solvent evaporation method. This study was designed to investigate the preparation, in vitro release,...
Paclitaxel(PTX)-loaded microspheres composed of poly(D,L-lactide-co-glycolide) (PLGA) were prepared by an O/W emulsion solvent evaporation method. This study was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a PTX-loaded microspheres system. Microspheres are characterized according to drug loading, size and shape. With a dynamic light scattering sizer and a transmission electron microscopy, it is shown that the PTX-loaded microspheres had a mean size of approximately 10.24 µm with narrow size distribution and a spherical shape. The in vitro release profiles indicate that the release of PTX from the microspheres exhibit a sustained release behavior. A similar phenomenon is observed in a pharmacokinetic study in rats, in which AUC of the microspheres formulation were 3.7-fold higher than that of PTX injection. The biodistribution study in mice showed that the PTX-loaded microspheres not only decreased drug uptake by liver, but also increased distribution of drug in lung. These results suggest that PTX-loaded microspheres may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i. v. administration of PTX.
Tissue distribution study of naringin in rats by liquid chromatography-tandem mass spectrometry.
Zou W, Yang C, Liu M … +1 more , Su W
Arzneimittelforschung · 2012 Apr · PMID 22270844 · Publisher ↗
Naringin (CAS 10236-47-2), a flavanone glucoside widely present in fruits of citrus plants, has received extensive studies on its potential effects on health benefits and was recently demonstrated to be a putative antitu...
Naringin (CAS 10236-47-2), a flavanone glucoside widely present in fruits of citrus plants, has received extensive studies on its potential effects on health benefits and was recently demonstrated to be a putative antitussive. In this study, we determined the tissue distributions of naringin and its metabolites (naringenin and naringenin's conjugates) in rats to examine whether they undergo selective uptake by specific organs. Naringin was administered orally to rats at the dose of 42 mg/kg and the concentrations of naringin and its metabolites in tissue compartments were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The areas under curve values in the individual tissues decreased as follows: stomach, small intestine, liver, trachea, muscle, kidney, lung, fat, heart, spleen, ovary, testis, brain for naringin; and liver, stomach, small intestine, kidney, trachea, lung, testis, heart, ovary, fat, spleen, muscle, brain for total naringenin (including free and its conjugates). Naringin and total naringenin were rapidly and widely distributed to all the tissues except brain in rats. They had difficulties in crossing the blood-brain barrier. There are no accumulations in rats. This study identifying naringin in several organs including lung and trachea may explain its effects as antitussive.
Synthesis, anticancer activity and radiosensitizing evaluation of some new 2-pyridone derivatives.
El-Said MS, El-Gazzar MG, Al-Dosari MS … +1 more , Ghorab MM
Arzneimittelforschung · 2012 Mar · PMID 22270843 · Publisher ↗
Based on the reported anticancer activity of 2-pyridone, a new series of 6-amino-5-cyano-1-(3-ethylphenyl)-2-oxo-4-substituted-1,2-dihydropyridine-3-carbo-nitriles 4a-p were synthesized and tested for in-vitro anticancer...
Based on the reported anticancer activity of 2-pyridone, a new series of 6-amino-5-cyano-1-(3-ethylphenyl)-2-oxo-4-substituted-1,2-dihydropyridine-3-carbo-nitriles 4a-p were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line and liver human tumor cell line (HEPG2). Radiosensitizing activity was also evaluated. The starting material 2-cyano-N-(3-ethylphenyl)-acetamide 3 was obtained via reaction of 3-ethyl aniline 1 with ethyl cyanoacetate under condition of fusion. Upon treatment of compound 3 with aromatic aldehyde and malononitrile in the presence of catalytic amount of piperidine yielded the corresponding 1,2-dihydropyridine derivative 4a-p. Also chromenes 5 and 6 were obtained in good yield via reaction of compound 3 with salicyladehyde under different condition. The chromene derivatives 5 and 6 were further reacted with malononitrile in NH4OAc, afford the corresponding chromenopyridones 7 and 8. The structures of the synthesized compounds 3-8 were confirmed by analytical and spectral data. Compounds 4d, 4e, 5 and 6 showed higher anticancer activity against EAC cell line with IC50 values (75.32, 20.77, 73.1 and 67.05 µM) compared to doxorubicin as positive control with IC50 value (68.13 µM), moreover, these compounds showed potent activity on HEPG2 cell line with IC50 values (26.5, 19.2, 39.3, 44.9 µM), respectively, compared to doxorubicin (CAS 29042-30-6) (38.46 µM) and their activity increased synergistically when combined with γ-radiation.
Effects of the multidrug resistance modulator HZ08 on the apoptosis pathway in human chronic leukaemia cell line K562/A02.
Cen J, Zhu YL, Yang Y … +5 more , Zhu JR, Fang WR, Huang WL, Li YM, Tao YF
Arzneimittelforschung · 2011 · PMID 22232851 · Publisher ↗
ōancer falls to respond to chemotherapy by acquiring multidrug resistance in over 90% of patients. A previous study revealed that multidrug resistance modulator HZ08 had great multidrug resistance reversal effect in vitr...
ōancer falls to respond to chemotherapy by acquiring multidrug resistance in over 90% of patients. A previous study revealed that multidrug resistance modulator HZ08 had great multidrug resistance reversal effect in vitro and in vivo. It could enhance adriamycin (doxorubicin) induced intrinsic apoptosis pathway and rectify cell cycle and some apoptosis related proteins in human breast resistant cancer MCF-7/ADM cells. This study detected Rh123 accumulation to assess the effect of HZ08 on P-glycoprotein function in human chronic leukaemia cell line K562/A02. Moreover, mitochondria membrane potential, cytochrome c release and caspase-3 activity were analyzed for HZ08 treatment with or without vincristine. Since pretreatment with HZ08 could also reverse the multidrug resistance to vincristine in K562/A02 cells, the individual influence of HZ08 was further detected on apoptotic regulator like Bcl-2, Bax, p53, cell cycle checkpoints and proliferation regulatory factors like survivin, hTERT, c-Myc, c-Fos, c-Jun. Finally, it revealed that HZ08 increased vincristine induced activation in intrinsic apoptosis pathway by inhibition of P-gp mediated efflux. In addition, the outstanding reversal effect of HZ08 should also attribute to its individual effect on apoptosis and proliferation related regulatory factors. It renders HZ08 possibility of application in pretreatment to reverse multidrug resistance while avoiding unexpected drug interactions and accumulative toxicity.
Pharmacokinetic and bioequivalence study of etoricoxib tablet in healthy Bangladeshi volunteers.
Shohag MH, Islam MS, Ahmed MU … +4 more , Joti JJ, Islam MS, Hasanuzzaman M, Hasnat A
Arzneimittelforschung · 2011 · PMID 22232850 · Publisher ↗
The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formula...
The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formulations meet the FDA criteria to assume bioequivalence. Twenty-four healthy volunteers were enrolled into this randomized, single-dose, 2-way crossover, open-label pharmacokinetic study. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa as a single dose of 60 mg tablets after 12 h overnight fasting, with a washout period of two weeks. Following oral administration, blood samples were collected at 0 (baseline), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0, and 120.0 h. Serum concentration of etoricoxib was assessed using a high performance liquid chromatographic-UV spectrometry procedure. The pharmacokinetic parameters were determined by the non-compartmental method. After administering a single dose of 60 mg of each etoricoxib formulation, the obtained mean (SD) values for the test and reference products were 1.26 (0.33) and 1.29 (0.35) microg/ml for Cmax; 3.25 (2.64) and 2.63 (1.40) h for t(max); 29.63 (8.31) and 30.40 (5.85) h x microg/ml for AUC0-120; and 31.84 (10.97) and 33.00 (8.10) h x microg/ml for AUC0-infinity, respectively. The mean t1/2 was found 27.99 (7.87) h and 29.84 (7.93) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. After analysis of variance, no period, sequence or formulation effects were observed for any pharmacokinetic property. The 90% confidence intervals of the test/reference mean ratios of the 1n-transformed AUC0-120, AUC0-infinity and Cmax mean values were 95.90% (85.37%-107.74 %), 94.69% (84.43%-106.20%) and 97.87% (85.54 %-111.98 %), respectively, which fell within the predetermined FDA bioequivalence range of 80%-125%. This single-dose study found that the test and reference formulations of etoricoxib met the regulatory criteria for bioequivalence in terms of both rate and extent of absorption.
Bioequivalence studies of film-coated tablet and chewable tablet generic formulations of montelukast in healthy volunteers.
Cánovas M, Arcabell M, Martínez G … +2 more , Canals M, Cabré F
Arzneimittelforschung · 2011 · PMID 22232849 · Publisher ↗
Two studies were conducted in order to assess the bioequivalence of montelukast (CAS 151767-02-1) 10 mg film-coated tablet (FCT) and 5 mg chewable tablet (CT) test formulations in comparison with the original brands. Und...
Two studies were conducted in order to assess the bioequivalence of montelukast (CAS 151767-02-1) 10 mg film-coated tablet (FCT) and 5 mg chewable tablet (CT) test formulations in comparison with the original brands. Under fasting conditions, healthy male and female volunteers received one 10 mg FCT or 5 mg CT orally as a single dose of a test or reference formulation. Both studies were designed as open-label, randomized, two-period, two-sequence, crossover studies with a 7-day washout interval. Plasma samples were collected up to 24 h after drug administration and montelukast levels were determined by a validated LC/ MS/MS method. Pharmacokinetic parameters were calculated using non-compartmental analysis and were statistically compared by analysis of variance for test and reference formulation. Bioequivalence between products was determined by calculating 90% confidence interval of the ratio test/reference of least-square means of logarithmically transformed Cmax and AUC0-t parameters. AUC0-infinity was also analysed to obtain additional information. The calculated 90% confidence intervals for the ratios of Cmax and AUC0-t parameters were 89.33-110.52 and 92.06-109.46, respectively, in the FCT study, and 91.58-101.86 and 92.15-98.83, respectively, in the CT study, which are all within the bioequivalence acceptance range of 80-125%. Based on the results, it can be concluded that the evaluated test FCT and CT formulations are bioequivalent to their respective reference formulation in terms of rate and extent of absorption.
Effect of Lactobacillus sporogenes on oral isoflavones bioavailability: single dose pharmacokinetic study in menopausal women.
Benvenuti C, Setnikar I
Arzneimittelforschung · 2011 · PMID 22232848 · Publisher ↗
PURPOSE OF THE STUDY: To verify the single dose bioavailability of two oral formulations of soy isoflavones, with and without lactobacilli, in menopausal women in antibiotic therapy. METHODS: Twelve menopause women (mean...
PURPOSE OF THE STUDY: To verify the single dose bioavailability of two oral formulations of soy isoflavones, with and without lactobacilli, in menopausal women in antibiotic therapy. METHODS: Twelve menopause women (mean age 54.3 years, BMI 25.0 kg/m2) participated in a controlled cross-over study. Reference and test treatments were: R = tablets containing soy isoflavones 60 mg (genistin 30 mg + daidzin 30 mg) + calcium and vitamin D3; E = R + 500 million vital spores of Lactobacillus sporogenes (E is Estromineral, a food supplement containing soy isoflavones 60 mg, calcium 141 mg and vitamin D3 5 microg). The design included 2 periods of 5 days of amoxicillin + clavulanate treatment with a 2-week wash-out. After each period alternatively a single dose of each formulation was given in randomised sequence. Genistein and daidzein were determined in plasma by HPLC, sampled 10 times within 24 h after dosing. RESULTS: Genistein pharmacokinetics parameters were higher after E than after R administration: peak plasma concentration (Cmax) +24.3%, area under the concentration curve (AUC0-24) +24.4% and mean residence time +11.0%. Daidzein Cmax and AUC showed a larger variability on R, evidenced by higher scatter from the mean on the formulation without lactobacilli. CONCLUSION: A trend is shown for a greater absorption of genistein from a formulation containing lactobacilli.
Pharmacokinetics and bioequivalence study of two digoxin formulations after single-dose administration in healthy Chinese male volunteers.
Zhang XY, Tian Y, Zhang ZJ … +2 more , Rui JZ, Cao XM
Arzneimittelforschung · 2011 · PMID 22232847 · Publisher ↗
The pharmacokinetics and relative bioavailability/bioequivalence of two formulations of digoxin (CAS 20830-75-5) were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an...
The pharmacokinetics and relative bioavailability/bioequivalence of two formulations of digoxin (CAS 20830-75-5) were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study design with a wash-out phase of 14 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose and digoxin plasma concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LCMS/MS) method. Based on the plasma concentration-time data of each individual during two periods, pharmacokinetic parameters, Cmax, AUC0-tau, AUC0-infinity and t1/2, were calculated by applying noncompartmental analysis. Pharmacokinetic data for test and reference formulations were analyzed statistically to evaluate bioequivalence of the two formulations. After oral administration, the values of Cmax Tmax, t1/2, AUC0-tau, AUC0-infinity for test and reference formulations were 2.61 +/- 0.98 and 2.68 +/- 1.09 ng/ mL, 1.0 +/- 0.4 and 1.0 +/- 0.4 h, 27.94 +/- 3.14 and 27.56 +/- 3.86 h, 28.57 +/- 4.99 and 28.77 +/- 6.53 ng x h/mL, 33.44 +/- 4.85 and 33.63 +/- 7.57 ng x h/mL, respectively. Both primary target parameters, AUC0-infinity and AUC0-tau, were tested parametrically by analysis of variance (ANOVA). Relative bioavailabilities were 102.5 +/- 19.2% for AUC0-infinity, 102.0 +/- 19.3% for AUC0-tau. Bioequivalence between test and reference formulations was demonstrated for both parameters, AUC0-infinity and AUC0-tau. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%, which means that the test formulation is bioequivalent to the reference formulation of digoxin.
Comparative pharmacokinetic and relative bioavailability study of coated and uncoated azithromycin powder for suspension in healthy Bangladeshi male volunteers.
Sultana TA, Islam MS, Bhuiyan NH … +6 more , Shohag MH, Ahmed MU, Naznin SR, Al Maruf A, Huq SM, Hasnat A
Arzneimittelforschung · 2011 · PMID 22164968 · Publisher ↗
Azithromycin (AZT; CAS 83905-01-5) is an efficient antibiotic and is widely prescribed in Bangladesh. The taste of uncoated AZT suspension is bitter. Although several taste masked oral suspensions of AZT are available in...
Azithromycin (AZT; CAS 83905-01-5) is an efficient antibiotic and is widely prescribed in Bangladesh. The taste of uncoated AZT suspension is bitter. Although several taste masked oral suspensions of AZT are available in Bangladesh, information regarding the bioavailability of these formulations in Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of two oral formulation of AZT (200 mg/5 ml) suspensions, the uncoated reference product and coated test product (Tridosil 200 mg/5 ml) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi male volunteers. A randomized, single-dose, two-way cross-over, open-label pharmacokinetic study was conducted in 24 healthy male volunteers after administration of a single dose of 500 mg AZT suspension under fasting condition following a washout period of three weeks. Blood samples were collected in different time intervals and analyzed for serum AZT concentration using a validated LC/MS/MS method. The pharmacokinetic parameters were determined by the non-compartmental method. From serum data, the obtained values for test and reference products were 383.21 +/- 11.59 and 432.28 +/- 7.22 ng/ ml for Cmax; 5677.47 +/- 1229.53 and 6144.56 +/- 1098.70 h x ng/ml for AUC(0-120); and 6085.29 +/- 1267.53 and 6694.15 +/- 1222.50 h x ng/ml for AUC(0-infinity), respectively. On analysis of variance, no period or sequence effects were observed for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax and AUMC(0-infinity). The 90% confidence intervals of the test formulation/reference mean ratios of the Intransformed Cmax, AUC(0-120) and AUC(0-infinity) mean values were found to be 87.89% to 89.36%, 87.96% to 95.71% and 86.77% to 94.29% respectively. In this single-dose study of AZT, it was found that the test formulation met the regulatory criteria for bioequivalence to the reference suspension formulation.
Determination of fenticonazole enantiomers by LC-ESI-MS/MS and its application to pharmacokinetic studies in female rats.
Feng Z, Zou Q, Tan X … +2 more , Che W, Zhang Z
Arzneimittelforschung · 2011 · PMID 22164967 · Publisher ↗
A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the determination of fenticonazole (CAS 72479-26-6) enantiomers in r...
A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the determination of fenticonazole (CAS 72479-26-6) enantiomers in rat plasma. Simple protein precipitation by acetonitrile was utilized for extracting analytes from the plasma samples. Chromatography separation was performed on a C18 analytical column (150 mm x 2.0 mm, 5 microm) with a mobile phase consisting of methanol-10 mM aqueous ammonium acetate (adjusted to pH 3.5 with acetic acid) (90:10, v/v) at a flow rate of 0.2 ml/min. Detection was carried out on a triple quadrupole mass spectrometer equipped with electrospray ionization (ESI) source, and operated in multiple-reaction monitoring (MRM) mode. The calibration curves were linear over the range 0.5 -200 ng/ml (r > 0.99). The relative recoveries of R-(-)-fenticonazole and its enantiomer were better than 85%. The intra- and inter-day precisions (R.S.D.%) and deviations of the assay accuracies were less than 10%. This newly developed and validated method was successfully applied to pharmacokinetic studies after administration at a single dose of 20 mg/ kg R-(-)-fenticonazole nitrate and its enantiomer to female rats per vagina. The Cmax value of S-(+)-fenticonazole was greater than that of R-(-)-fenticonazole by 1.36-fold, whereas, the t(1/2) beta and MRT values of R-(-)-fenticonazole were longer than those of its enantiomer by 1.95- and 1.24-fold. The results indicated that S-(+)-fenticonazole was faster in absorption and elimination in female rat. But, the Tmax and AUC(0-12) values for each of fenticonazole enantiomers were not significantly different.
Nanoformulation of siRNA silencing Bcl-2 gene and its implication in cancer therapy.
Jagani HV, Josyula VR, Hariharapura RC … +2 more , Palanimuthu VR, Gang SS
Arzneimittelforschung · 2011 · PMID 22164966 · Publisher ↗
The purpose of this research work was to prepare poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for delivery of siRNA (small interfering RNA) for silencing anti-apoptotic Bcl-2 gene in cancerous cells by using the d...
The purpose of this research work was to prepare poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for delivery of siRNA (small interfering RNA) for silencing anti-apoptotic Bcl-2 gene in cancerous cells by using the double emulsion solvent diffusion (DESE) method. Overexpression of Bcl-2 is often seen in a wide variety of human cancers. This prevents the induction of programmed cell death (i.e., apoptosis) in cancerous cells. It is also reported that over-expression of Bcl-2 contributes to resistance in chemotherapy and inhibits the apoptosis induced by chemotherapeutic agents. Agents antagonizing the anti-apoptotic Bcl-2 protein have been shown to restore normal apoptotic processes in cancer cells. RNA interference (RNAi) has emerged as an efficient and selective technique for gene silencing, siRNA mediated gene silencing has been used in a wide variety of disease condition. PLGA nanoparticles were able to completely bind siRNA and to provide protection for siRNA against nuclease degradation. In vitro cell culture studies subsequently revealed that PLGA nanoparticles with adsorbed siRNA could efficiently silence the targeted anti-apoptotic Bcl-2 gene in mammalian cells. In vivo studies results showed that siRNA was effectively delivered through nanoparticles and there was significant decrease in the tumor volume.
Protective effects of tripterygium glycoside-loaded solid lipid nanoparticles on male reproductive toxicity in rats.
Xue M, Jiang ZZ, Wu T … +5 more , Yan M, Liu JP, Mu XM, Su YW, Zhang LY
Arzneimittelforschung · 2011 · PMID 22164965 · Publisher ↗
The protective effects of tripterygium glycoside-loaded solid lipid nanoparticles (TG-SLNs) on male reproductive toxicity were investigated in rats. Thirty-six male Sprague-Dawley rats were randomly divided into three gr...
The protective effects of tripterygium glycoside-loaded solid lipid nanoparticles (TG-SLNs) on male reproductive toxicity were investigated in rats. Thirty-six male Sprague-Dawley rats were randomly divided into three groups of 12: control group, tripterygium glycoside (TG) group, and TG-SLN group. After the animals had been orally administered with the substances for 28 consecutive days, their sperm count and sperm motility, organ coefficients, serum testosterone levels, testicular ultrastructure, and reproductive ability were observed. The results showed that the sperm motility rate in the TG group was only 3%, whereas the rates in the TG-SLN and control groups were 33% and 71%, respectively. Compared with those in the control group, the motion counts of path velocity, track speed, progressive velocity, straightness, linearity, beat cross frequency, amplitude of lateral head displacement, and sperm concentrations in the TG-SLN group were not significantly different while those in the TG group significantly decreased (p < 0.01). TG-SLNs did not cause testicular atrophy and instead maintained normal serum testosterone levels. The effect of TG-SLNs on the testicular ultrastructure was very evident; the morphologies of Sertoli, spermatogonial, mitochondrial, and sperm cells were normal. In terms of reproductive ability, one rat (17%) from the TG-SLN group and five rats (83%) from the control group became pregnant, whereas none of the rats from the TG group became pregnant. These data indicate that TG-SLNs have potentially protective effects on male reproductive toxicity in rats.
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