The oral bioavailability of itraconazole is variable and low in fasting state. This is mainly due to the low solubility of this drug. Bioavailability can be improved by changing the formulation and it is general that the liquid preparations show greater bioavailability than the solid dosage forms such as tablets and capsules do. Benzyl alcohol-water binary mixture showed the excellent solubilizing capacity for itraconazole but the release of the drug from the preparation needs to be enhanced. In this study, various nonionic surfactants and hydrophilic polymers, poloxamers, were screened to investigate their effects on the releasε of itraconazole from the liquid preparations. Poloxamer 407 showed the most enhancing effect on the drug release and the release rate was proportional to thε amount of poloxamer 407 added. A liquid preparation of itraconazole, consisting of benzyl alcohol/water/poloxamer 407 ternary solvent system, releasεd more than 80% of the total drug amount at 5 min and showεd the possibility of a new formulation development.
We have surveyed the epidemiology of functional dyspepsia in 7 cases of Children and investigated the therapeutic effect on Functional Dyspepsia following 4 weeks medication of Naesowhajung-tang using Electrogastrogram. The Results were as followings: 1. Sex ratio are 6 males, 1 female; their mean ages, $9.0{\pm}1.41(7-11years)$; length, $137.2{\pm}13.86cm$; body weight, $35.3{\pm}l1.34kg$. 2. Most of subjects have a normal growth state. But one case have severe growth disturbance. Familial tendency for this disease is noted in 85.8%. 3. Abdominal pain was seen in 100% of subjects. The indicated symptom was lowed in order of abdominal pain(100%), nausea vomiting(71.43%), general fatigue(65.34%), vertigo headache(57.14%), belching(55.38%), etc. 4. The EGG finding after treatment was improved in 53%, aggrevated in 43. In cases, postprandial improvement was more remarkable than fasting improvement. Common cold and antibiotics seems to have functioned as an aggrevating factor on gastric motility. From the above results, Naesowhajung-tang seems to have been used in the treatment of functional dyspepsia for children.
Proceedings of the Korean Society of Toxicology Conference
/
2006.11a
/
pp.80-86
/
2006
Bioequivalence is a term in pharmacokinetics used to access the expected in vivo biological equivalence of two proprietary preparations of a drug. Bioequivalence studies are usually performed for generic drugs. Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent and their bioavailabilioes after administration in the same molar dose are similar. Bioequivalence is usually accessed by single dose in vivo studies in healthy volunteers and the reference product is usually the innovator product that is marketed. Regulatory definition of bioequivalence is based on the statistical analysis of thebioavailability of the reference and test product. In general, two products are evaluated as bioequivalent if the 90% confidence interval of the relative mean Cmaxand AUC of the test to reference product are within 80.00% to 125.00% in the fasting state. Key process in bioequivalence study is development and validation of bioanalytical method, determination of the drug concentration in the biosamples (usually plasma or serum) obtained from volunteers, calculation of the pharmacokinetic parameters and statistical analysis of the pharmacokinetic parameters. Although current guidelines and regulations do not require the bioequivalence studies to be done under good laboratory practice (CLP), the issues to perform the bioequivalence studies under GLP environment is emerged both from the regulatory and industry side. GLP perspectives of bioequivalence studiesare needed to be discussed in respect to achieve quality assurance in bioequivalence studies.
Yan, Xiaogang;Zhang, Wei;Cheng, Jianbo;Wang, Runlian;Kleemann, David O.;Zhu, Xiaoping;Jia, Zhihai
Asian-Australasian Journal of Animal Sciences
/
v.21
no.6
/
pp.853-860
/
2008
This experiment was conducted to study the effects of chromium (Cr), dietary crude protein (CP) level and potential interactions between these two factors on growth rate and carcass response, insulin activity and lipid metabolism in lambs. Forty-eight, 9-week-old weaned lambs (Dorper$\times$Small-tail Han sheep, mean initial body weight = $22.96kg{\pm}2.60kg$) were used in a $2{\times}3$ factorial arrangement of supplemental Cr (0 ppb, Cr0; 400 ppb, Cr1; or 800 ppb, Cr2 from chromium yeast) and CP levels (157 g/d to 171 g/d for each animal, LP; or 189 g/d to 209 g/d for each animal, HP). Growth data and blood samples were collected at the beginning and end of the feed trial, after which the lambs were killed. Both Cr additive groups and the HP group increased final weight and average daily gain, especially the Cr1 and HP group (p<0.01). HP increased pelvic fat weight (p<0.05), fat thickness of the 10th rib (p<0.05), longissimus muscle area (p<0.01) and rate of deposition of intramuscular fat (p<0.01). Supplemental Cr decreased the rate of deposition of intramuscular fat (p<0.05). Fasting insulin level and the ratio of insulin to glucose were lower with Cr1 than other groups, but with no significant difference. Glucose concentration was not affected by any treatment. Nonesterified fatty acids increased in the Cr1 (p<0.05) and HP (p<0.05) conditions and there was a significant $Cr{\times}CP$ interaction (p<0.05). Cr1 decreased triglycerides (p<0.05) and total cholesterol (p = 0.151) and HP increased high-density lipoprotein cholesterol (p<0.05). Cr1 decreased lipoprotein lipase activity in subcutaneous adipose tissue (aLPL, p<0.05) and the ratio of aLPL to lipoprotein lipase activity in skeletal muscle (mLPL, p = 0.079). mLPL and hepatic lipase (hHL) were not affected by any treatment. In the present study, Cr had limited effects on growth rate and carcass response, whereas Cr and CP had some notable effects on plasma metabolites and enzyme activities. Cr has a potential effect on energy modulation between lipid and muscle tissue. In addition, few $Cr{\times}CP$ interactions were observed.
Eighteen lambs were used to determine the effects of zinc (Zn) level and source on Zn status and immune function during both normal conditions and conditions of physiologic stress. Treatments consisted of a basal diet (27.6 mg of Zn/kg), and the basal diet supplemented with 25 mg of Zn/kg, added as either zinc oxide or zinc methionine. The basal diet was a corn-cottonseed hull-isolated soy protein- based diet (14% CP). Lambs were weighed and blood samples taken at 28-d intervals for determination of serum Zn and alkaline phosphatase activity. Weights and serum Zn were similar (p > 0.10) among treatments at all sampling days. To evaluate immune responses and Zn status during conditions of physiologic stress lambs were administered 100 I.U. of adrenocorticotrophin (ACTH) on d 112 and feed was withheld for 48 h. Cortisol levels were elevated (p < .01) 5 h post ACTH injection, but had returned to initial levels after 48 h. Lymphocyte blastogenesis ([$^3H$]-thymidine incorporation) on d 112 (prior to ACTH injection) and 114 was unaffected (p > .10) by dietary treatment. However, blastogenesis in response to pokeweed mitogen was greater (p < .0001), whereas the response to phytohemagglutinin was reduced (p < .01) following ACTH administration and fasting. Antibody response to administration of porcine red blood cells was unaffected (p > .05) by dietary treatment. These results indicate that, given the Zn concentration of the basal diet, there was no enhancement of immune function by supplemental Zn, either before or after lambs were subjected to stress.
Background & Aims : The aim of this study was to investigate the change of dominant power with observation of gastric myoelectrical activity and its parameter linkage in electrogastrography. Methods : Electrogastrography was performed on a total of 123 subjects (113 patients with functional dyspepsia, 10 healthy controls) for 30 min in fasting state and 50 min in postprandial state. Average myoelectrical activity per frequency and accumulated electrical activity of 5 min duration in each bradygastria, normogastria, and tachygastria were measured at the moment of frequency switchover of slow wave. Assumed parameter linkages were also investigated among dominant frequency, % of normal regularity, and dominant power (or power ratio). Results : Average myoelectrical activity per frequency was highest in bradygastria (mean 1.10-1.47 Volt/s), next highest in normogastria (mean 0.50-0.82 Volt/s), and lowest in tachygastria (mean 0.44-0.47 Volt/s). Average accumulated myoelectrical activity was highest in normogastria (mean 114.90-126.29 Volt/ss), next highest in tachygastria (mean 71.02-90.00 Volt/ss), and lowest in bradygastria (mean 12.93-51.94 Volt/ss). Significance of parameter linkages were noted in dominant frequency (p< 0.01) and in % of normal regularity (p< 0.01), but not in dominant power in case of frequency shift from bradygastria to normogastria (p=0.376). Conclusion : Dominant power is not a parameter that reflects the gastric myoelectrical activity related with only gastric contraction. Bradygastric dominant power does not follow the inter-parameter linkage of electrogastrography for gastric motility assessment.
A study was carried out to find out the relationship between arginine vasopressin (AVP) release and plasma osmolality in 15 young men (age: 21.4 yr). After an overnight fasting, wale. (20 ml/kg) was imbibed, and venous blood and urine samples were collected every 30 min for 90 min. then 5% saline was infused (0.06 ml/min/kg) for 120 min. AVP was extracted on Sep-Pak column and measured by radioimmunoassay. Under basal condition, plasma osmolality (pOsm), AVP (pAVP) and aldosterone (pAldo) levels were 286.5 mOsm/kg, 1.1 pg/ml, and 140 pg/ml, respectively. pAVP became undetectable during maximum water diuresis, and increased in response to hypertonic saline infusion. pAVP level began to increase when pOsm was above 280 mOsm/kg. Changes in urinary AVP excretion (uAVP) was parallel to pAVP levels. The fall in pAVP was followed by a decrease in uAVP, uOsm and an increase in free water clearance, while the later rise in pAVP was followed by an increase in uAVP, uOsm and a decrease in free water clearance. When pooling all data together, relationships between pAVP and pOsm, and uAVP and uOsm were best expressed by an exponential relationship (r=0.78, 0.86, respectively). pAldo level decreased to 71 pg/ml after water ingestion, and decreased further to 30 pg/ml 2 hr after 5% saline infusion. Even at the same pNa, pAldo level during dehydration state was significantly higher than during hydration state. Negative exponential relation (r=-0.59) was observed between pAldo and pNa. Response to change in body fluid volume was greater in aldosterone than in AVP release.
The Ultrasonographic method alas been widely applied to evaluating gastric motility with safety and reproducibility ill human medicine but few reference to its use in veterinary medicine is appeared. Therefore, in this study, the gastric motility was evaluated with ultrasonography by the cri-terion of mean cycle lime, short and lony axis and the area of pyloric antrum in dogs, fed with liquid of semisolid meals. Furthermore, the animals were evaluated for the effect of metoclopramide on the motility of pyloric antrum. Healthy 5 mongrel male dogs were fed with either 400 ml of milk a: a liquid meal or a mixed meal of 200 ml of milk with two pieces of bread as a semisolid meal. Mean cycle time of pyloric antrum of dogs was significantly delayed after feeding either of liquid and , semi- solid meals(P<0.05), alls it was returned to the fasting state at 60 min. after feeding of liquid meal and 160 min. after feeding of semisolid meal. Mean area of pyloric antrum of dogs was gradually decreased and was returned to the lasting state at 80 min. in doss fed liquid meal. but 1600 min. in dog\ulcorner fed semisolid meal. The administration of metoclopramide (1.0 mg/kg of of B.W.) accelerated the mean cycle time of pyloric antrum from 20 mill. to 60 min. after feeding of liquid meal and from 40 min. to 120 min. after feeding of semisolid meal. From this study, the ultrasonography was confirmed as a valuable diagnostic method leer evaluating the gastric motility and gastric area in dogs. It is non-invasive, safe and reproducible, and provides a method for the study of the effect of drugs and diseases states on gastric motility.
The effects of chromium (Cr), dietary crude protein (CP) level, and potential interactions of these two factors were investigated in term of energy metabolism in lambs. Forty-eight 9-week-old weaned lambs (Dorper${\times}$Small-tail Han sheep, male, mean initial body weight = 22.96 kg${\pm}$2.60 kg) were used in a 2${\times}$3 factorial arrangement of supplemental Cr (0 ${\mu}g$/kg, 400 $\mu{g}$/kg or 800 ${\mu}g$/kg from chromium yeast) and protein levels (low protein: 157 g/d to 171 g/d for each animal, or high protein: 189 g/d to 209 g/d for each animal). Blood samples were collected at the beginning and end of the feeding trial. The lambs were then sacrificed and tissue samples were frozen for further analysis. Chromium at 400 ${\mu}g$/kg decreased fasting insulin level and the ratio of plasma insulin to glucagon, but these differences were not statistically significant; in contrast, chromium at 800 ${\mu}g$/kg increased the ratio significantly (p<0.05). Protein at the high level increased plasma tumor necrosis factor $\alpha$ (TNF-$\alpha$) level (p = 0.060). Liver glycogen content was increased significantly by Cr (p<0.05), which also increased liver glucose-6-phosphatase (G-6-Pase) and adipose hormone-sensitive lipase (HSL) activity. At 400 ${\mu}g$/kg, Cr increased muscle hexokinase (HK) activity. High protein significantly increased G-6-Pase activities in both the liver (p<0.05) and the kidney (p<0.05), but significantly decreased fatty acid synthase (FAS) activity in subcutaneous adipose tissue (p<0.05). For HSL activity in adipose tissue, a Cr${\times}$CP interaction (p<0.05) was observed. Overall, Cr improved energy metabolism, primarily by promoting the glycolytic rate and lipolytic processes, and these regulations were implemented mainly through the modulation by Cr of the insulin signal transduction system. High protein improved gluconeogenesis in both liver and kidney. The interaction of Cr${\times}$CP indicated that 400 $\mu{g}$/kg Cr could reduce energy consumption in situations where energy was being conserved, but could improve energy utilization when metabolic rate was increased.
Journal of the Korean Society of Food Science and Nutrition
/
v.29
no.3
/
pp.466-470
/
2000
The current study was undertaken to determine the prolinged effects of fasting-refecding on the lipoprotein lipase (LPL) activity and lipogenesis of adipose tissus in male Sprague-Dawley rals and to investigate the effects of various degrecs of food restriction during refeeding on the LPL activity and lipogenesis. The control group (n=5) was fed ad libitum and killed in the fed state at the beginning of the experiment. All rats except conteol group were fasted for 2 days (n=50). Five rats were killed at the end of fasting and others (n=45) were refed either ad libitum (ad libitum group) or mildly restricted (20% food restricted group), or esverely restricted diet (40% food restricted group). Rats were killed on the day of 7th, 14th, and 21st of refeeding. Lipogenesis was determined by the amount of glucose converted to the total lipid. Body weight and epididymal adipose tissue weight returned to control states by 5 days in ad libitym group and by 14 days in 20% food restricted group. As expected, in 40% food restriction during refeeding weight and epididymal adipose tissue weight did not rcturn to control states until day 21. On day 21 after refeeding, the serum total cholesterol concentration of ad libitum group was significantly (p<0.05) higher than that of control group. The serum HDL-C concentration of 40% food restricted group during refeeding was significantly (p<0.05) higher than that of control group. However, there were no significant dif-ferences in serum HDL-C/total cholesterol (TC) ratio and trigluceride concentration among the groups. Fasting for 2 days decreased lipogenesis and LPL activity (p<0.05). On day 21 after refecding, the lipogencsis of ad libitum group was significantly (p<0.05) lower than that of control group. The lipogenesis of 40% food restricted group during refeeding was significantly (p<0.05) higher than that of conrtol group. Ad libitum group and 20% food restricted group during refecding allowed heparin-releasable (HR) LPL or total extractable (TE) LPL activity to return to control states. 40% food restricted group during refeeding delayed the return of HR-LOL or TE-LPL activity to return to control states until day 21 of refeeding. These results suggest that food restriction during refeeding can partially or completely prevent the overshoot of LPL activity, and this may influence the rate of lipid accumulation in adipose tissue during refeeding.
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