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Bioavailability Study (bioavailability + study)
Selected AbstractsNeuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficitsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Qun Wang Abstract Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death. © 2005 Wiley-Liss, Inc. [source] A solid-state approach to enable early development compounds: Selection and animal bioavailability studies of an itraconazole amorphous solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010David Engers Abstract A solid-state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Itraconazole (ITZ) was chosen as a model crystalline compound displaying poor aqueous solubility and low bioavailability. Solid dispersions were prepared with different polymers (PVP K-12, K29/32, K90; PVP VA S-630; HPMC-P 55; and HPMC-AS HG) at varied concentrations (1:5, 1:2, 2:1, 5:1 by weight) using two preparation methods (evaporation and freeze drying). Physical characterization and stability data were collected to examine recommended storage, handling, and manufacturing conditions. Based on generated data, a 1:2 (w/w) ITZ/HPMC-P dispersion was selected for further characterization, testing, and scale-up. Thermal data and computational analysis suggest that it is a possible solid nanosuspension. The dispersion was successfully scaled using spray drying, with the materials exhibiting similar physical properties as the screening samples. A simple formulation of 1:2 (w/w) ITZ/HPMC-P dispersion in a capsule was compared to crystalline ITZ in a capsule in a dog bioavailability study, with the dispersion being significantly more bioavailable. This study demonstrated the utility of using an amorphous solid form with desirable physical properties to significantly improve bioavailability and provides a viable strategy for evaluating early drug candidates. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3901,3922, 2010 [source] Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesteroneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Catherine Tuleu Abstract A pellet formulation of progesterone in a self-emulsifying system (SES) was prepared by the process of extrusion/spheronization to provide a good in vitro drug release (100% within 30 min, T50% at 13 min). A three-way randomized crossover study was performed in six fasted male beagle dogs with these pellets and the same SES liquid formulation, both contained in a hard shell capsule, and an aqueous suspension. The same dose of progesterone (16 mg) in pellets and in the SES liquid formulation resulted in similar AUC, Cmax and Tmax values, estimated from progesterone plasma levels by 125I radioimmunoassay. Although the maximum absorption was slightly retarded (0.5 to 1 h) by SES (pellets and liquid), AUC and Cmax were approximately seven and nine times greater then those obtained when an aqueous suspension formulation of the same dose of progesterone was administered to the same dogs. These results showed that it was possible to improve the bioavailability of the poorly soluble, poorly permeable progesterone when administered in SES. Moreover, presenting the progesterone in the form of a pellet did not prevent the release of the drug in vivo. These data demonstrate the utility of extrusion/spheronization in delivering a nonaqueous system in a novel solid dosage form. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1495,1502, 2004 [source] Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability studyBIOMEDICAL CHROMATOGRAPHY, Issue 7 2010Ronilson Agnaldo Moreno Abstract In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether,dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5,mm NH4OH on a Gemini Phenomenex C8 5,,m column (50 × 4.6,mm i.d.) in 5.0,min/run. The method fitted to a linear calibration curve (0.05,10,ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0,mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine®, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and AUC ratios were all within the 80,125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption. Copyright © 2009 John Wiley & Sons, Ltd. [source] Liquid chromatography tandem mass spectrometry method for determination of bisoprolol in human plasma using d5-bisoprolol as the internal standardBIOMEDICAL CHROMATOGRAPHY, Issue 6 2010Gang-yi Liu Abstract A simple, reliable and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol was developed and validated for quantification of bisoprolol in human plasma. The sample was pretreated with a simple procedure of protein precipitation and an isotope-labeled d5-bisoprolol was used as internal standard. The chromatographic separation was performed on a Capcell Pak C18 MG III column (100,mm × 2.0,mm, 5,µm). The protonated ion of the analyte was detected in positive ionization by multiple reaction monitoring mode. The mass transition pairs of m/z 326.3 , 116.3 and m/z 331.3 , 121.3 were used to detect bisoprolol and the internal standard, respectively. Linearity, accuracy, precision, recovery, matrix effect, dilution test and stability were evaluated during method validation over the range of 0.5,100,ng/mL. The validated method was successfully applied to analyze human plasma samples in a bisoprolol bioavailability study. Copyright © 2009 John Wiley & Sons, Ltd. [source] Likelihood Analysis for the Ratio of Means of Two Independent Log-Normal DistributionsBIOMETRICS, Issue 2 2002Jianrong Wu Summary. Existing methods for comparing the means of two independent skewed log-normal distributions do not perform well in a range of small-sample settings such as a small-sample bioavailability study. In this article, we propose two likelihood-based approaches,the signed log-likelihood ratio statistic and modified signed log-likelihood ratio statistic,for inference about the ratio of means of two independent log-normal distributions. More specifically, we focus on obtaining p -values for testing the equality of means and also constructing confidence intervals for the ratio of means. The performance of the proposed methods is assessed through simulation studies that show that the modified signed log-likelihood ratio statistic is nearly an exact approach even for very small samples. The methods are also applied to two real-life examples. [source] Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2002P. Delrat Abstract A new modified release (MR) formulation containing 30 mg of gliclazide was developed to obtain a better predictable release of the active principle and to allow once-daily dosing regimen. An absolute bioavailability study was carried out to characterise the performance of the new formulation and the food-effect was also investigated in a separate study. Both studies were single dose, randomised, open label, two way cross over studies with a wash out period between doses. For the bioavailability study, each volunteer received 30 mg of gliclazide given either as a 1 h intravenous infusion or as a 30 mg MR tablet. For the food-effect study, the treatment was given either fasted or 10 min after the start of a standardised Melander breakfast. Blood samples were collected up to 72 h after administrations and plasma samples assayed for gliclazide concentrations using a reverse-phase HPLC method with UV detection. Mean absolute bioavailability of gliclazide was 97% and ranged between 79 and 110% showing complete absorption. A similar moderate to low variability was observed after IV and oral administration showing the MR formulation did not add to the overall variability which is solely due to the disposition parameters, in particular metabolism of gliclazide. No significant difference was observed in tmax, t1/2z, Cmax and AUC of gliclazide after administration of the 30 mg MR tablet under fasted and fed conditions. In conclusion, after single oral administration of a 30 mg MR tablet, gliclazide was completely absorbed both under fasted and fed conditions. A consistent and optimal release of gliclazide from this formulation leads to a low to moderate overall variability of its pharmacokinetic parameters. Diamicron 30 mg MR can be given without regards to meals i.e. before, during or after breakfast. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||