Microspheres of felodipine, which is one of the calcium channel blocker using a mixture of Eudragi $t^{R}$ RL, L, E, and cellulose on the base of Eudragi $t^{R}$ RS were investigated. Cremopho $r^{R}$ was added to each preparation of polymers in order to increase the release of felodipine from microspheres. Felodipine-loaded microspheres were prepared by a solvent evaporation method, which is based on dispersion of methylene chloride containing felodipine and polymers in 0.5 w/v % polyvinyl alcohol solution. The average diameter based on the size distribution of the felodipine-loaded microspheres was observed to be ca. 40-55 ${\mu}{\textrm}{m}$. A good and smooth surface were showed in all types of the microspheres. The amount of felodipine loaded was over 90 w/w % in all types of microspheres. The dissolution profiles of felodipine from microspheres were similar with each type of polymer, and about a 60 w/w % of the total amount of felodipine loaded to microsphere was released within 7 hours. Dissolution rate of felodipine from the microsphere was increased by addition of Cremophor. After oral administration of the felodipine-loaded microspheres in PVA solution and felodipine alone in PEG solution to rats, respectively, the pharmacokinetic study revealed that the Tmax values of the microspheres were observed in the range of 0.67~l.0 hr while that of the felodipine solution was obtained 0.33 hr. In addition, the AUC of the microspheres at 0 to 7 hr was remarkably increased in comparison to that of felodipine solution. These results revealed that the microspheres based on Eudragit RS could be a good candidate for the controlled release drug delivery system for felodipine.e.e.e.
Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration $(C_{max})$ and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.
Ji-Hyock Yoo;Hui-Seon Kim;Mi-jin Kim;Jung-Ok Woo;Ho-yang Choi;Sung-Chul Kim
Journal of Applied Biological Chemistry
/
v.65
no.4
/
pp.349-355
/
2022
In this study, we sought to identify a soil stabilizer that can be applied to paddy fields vulnerable to arsenic (As) pollution. To this end, we conducted a pot experiment in which we evaluated the effects of different stabilizers on the bioavailability of As in paddy soil. As candidate stabilizers, we assessed calcium superphosphate (CSP), sulfur, and steel slag, which were applied at the rates of 0.7 and 1.4, 0.1 and 0.2, and 7.0 and 14.0 Ma ha-1, respectively. On day 67 after rice transplantation, we detected significantly lower concentrations of As in the solutions of paddy soil treated with 1.4 Ma ha-1 CSP (96.9 ㎍ L-1) and 0.2 Ma ha-1 sulfur (207.2 ㎍ L-1) compared with the As concentrations in control (314.5 ㎍ L-1) and steel slag-treated (268.6-342.4 ㎍ L-1) soil. Compared with the As concentrations in control brown rice (0.16 mg kg-1), concentrations in brown rice were lowest in the pots treated with 1.4 Ma ha-1 CSP (0.09 mg kg-1). Furthermore, in response to CSP treatments, we detected increases in the weight of rice grains (50.0-50.4 g/pot) compared with the control (40.4 g/pot) and other treatments (26.9-48.1 g/pot), which we speculate could be attributed to the reduction in As toxicity to rice owing to a decline in soil solution As contents and the fertilization effect of the CSP treatment. Collectively, our findings indicate a high-level application of CSP (1.4 Ma ha-1) to paddy soil has a comparatively beneficial effect in mitigating the bioavailability of As.
Lee Ok-Hee;Kim Bo-Ha;Lee Seung-Whan;Park Seung-Uk;Park Chang-Jung;Moon Jong-Wha;Chung Yong-Sam
Journal of Nutrition and Health
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v.39
no.3
/
pp.252-263
/
2006
Zinc is an antioxidant trace mineral, scavenging free radicals and known to be involved in inflammatory reactions. The prevalence of atherogenic diseases such as coronary heart disease (CHD) are increasing in Korean adults of middle age and elderly. The increased cell damage from free radicals and inflammation have been implicated in etiology of CHD, and the evidence is accumulating that low zinc status is involved in the prevalence of this inflammatory atherogenic disease. However, little is known about the zinc status of Korean CHD and its relationship with dietary zinc intake and zinc bioavailabilty. In this study the serum zinc levels of male patients with CHD over 40 yrs. were compared with that of healthy adult males and its associations with dietary zinc intake and zinc bioavailabilty affecting factors were examined. Serum zinc level was measured by HANARO research reactor using neutron activation analysis (NAA) method. The overall proportion of patients with zinc deficiency, serum zinc concentrations below $74.0{\mu}g/dL$ was 32.8% compared to the 10.3% in healthy group. The average serum zinc levels were $80.7{\mu}g/dL\;and\;88.3{\mu}g/dL$ in patients and healthy group, respectively, showing significantly low zinc status in CHD patients compared to healthy group. The intake of nutrients such as energy, carbohydrate, iron, and copper of CHD patients was significantly higher compared to that of the healthy group. In addition, the intake of calcium, iron, and protein from vegetable foods was significantly higher in CHD patients than that of healthy group. The dietary zinc intake was $12.7{\pm}4.5mg$ and $11.5{\pm}6.9mg$ in CHD patients and control group, respectively, which showed no difference. The phytate intake of patients group, which is 1389.0 mg, was significantly higher than the control group which showed 1104.8 mg. However, the ratio of phytate: zinc or phytate * calcium. zinc per 1000 kcal energy intake did not show any difference between two groups. The serum zinc levels did not show any correlation with zinc or factors that affect the bioavailability of zinc. The dietary factors influencing the zinc status were not found in CHD patients.
Journal of the Korean Society of Food Science and Nutrition
/
v.30
no.4
/
pp.739-746
/
2001
To assess the nutrient intakes and diet quality of middle school students living in Kangneung area a dietary survey using th 3-day food record was conducted with 226 subjects. Mean daily energy intake was 2114$\pm$502 kcal with 61.6% of energy supplied by carbohydrate 16.4% by protein and 22.0% by fat. As well as insufficiencies in calcium and iron intakes the bioavailability of calcium and iron consumed is considered to low because most of them came from plant origins. For calcium iron vitamin A and vitamin B$_2$the proportions of subjects with intake levels less than 75% of RDA were all over 46%. The mean adequacy ratio(MAR) an index of overall dietary quality was 0.70 for males and 0.73 for females. The indexes of nutritional quality (INQ) were over 1 for most nutrients except 4 nutrients; 0.48 of calcium 0.64 of iron 0.73 of vitamin A and 0.79 of vitamin B$_2$. Nutrient intake levels less than 75% of RDA may be appropriate as a criteria for insufficiency of nutrient intakes. Based on these results it is evident that some of middle school students in Kangneung area did not consume enough nutrients especially calcium iron and vitamin A.
Journal of Korean Home Economics Education Association
/
v.17
no.3
s.37
/
pp.35-52
/
2005
To assess the food habits, the nutrient intakes and diet quality of high school students living in Chuncheon area. a dietary survey using a questionnaire and 24hr recall method was conducted with 318 subjects. $30.8\%$ of the subjects often skipped breakfast and $28.0\%$ had snacks over once per day. Mean daily energy intake was $1740\pm712kca1\;with\;61.1\%$ of energy supplied by carbohydrate, $16.0\%$ by protein and $23.1\%$ by fat. As well as insufficiencies in calcium and iron intakes, the bioavailability of calcium and iron consumed is considered to be low because most of them came from plant origins. For calcium, iron and riboflavin, the proportions of subjects with intake levels less than $75\%$ of RDA were all over $68\%$. The mean adequacy ratio(MAR), an index of overall dietary quality was 0.79 for males and 0.78 for females. The indexes of nutritional quality(INQ) were over 1 for most nutrients except 3 nutrients: 0.67 of calcium, 0.82 of iron, 0.90 of riboflavin. Nutrient intake levels less than $75\%$ of RDA may be appropriate as a criteria for insufficiency of nutrient intakes. Based on these results, it is evident that some of high school students in Chuncheon area did not consume enough nutrients, especially calcium, iron and riboflavin.
This study was conducted to evaluate the relative bioavailability (RBV) of 25-hydroxycholecalciferol (25-OH-$D_3$) to cholecalciferol (vitamin $D_3$) in 1- to 21-d-old broiler chickens fed with calcium (Ca)- and phosphorus (P)-deficient diets. On the day of hatch, 450 female Ross 308 broiler chickens were assigned to nine treatments, with five replicates of ten birds each. The basal diet contained 0.50% Ca and 0.25% non-phytate phosphorus (NPP) and was not supplemented with vitamin D. Vitamin $D_3$ was fed at 0, 2.5, 5.0, 10.0, and $20.0{\mu}g/kg$, and 25-OH-$D_3$ was fed at 1.25, 2.5, 5.0, and $10.0{\mu}g/kg$. The RBV of 25-OH-$D_3$ was determined using vitamin $D_3$ as the standard source by the slope ratio method. Vitamin $D_3$ and 25-OH-$D_3$ intake was used as the independent variable for regression analysis. The linear relationships between the level of vitamin $D_3$ or 25-OH-$D_3$ and body weight gain (BWG) and the weight, length, ash weight, and the percentage of ash, Ca, and P in femur, tibia, and metatarsus of broiler chickens were observed. Using BWG as the criterion, the RBV value of 25-OH-$D_3$ to vitamin $D_3$ was 1.85. Using the mineralization of the femur, tibia, and metatarsus as criteria, the RBV of 25-OH-$D_3$ to vitamin $D_3$ ranged from 1.82 to 2.45, 1.86 to 2.52, and 1.65 to 2.05, respectively. These data indicate that 25-OH-$D_3$ is approximately 2.03 times as active as vitamin $D_3$ in promoting growth performance and bone mineralization in broiler chicken diets.
Rahman, M.M.;Nakagawa, T.;Niimi, M.;Fukuyama, K.;Kawamura, O.
Asian-Australasian Journal of Animal Sciences
/
v.24
no.7
/
pp.940-945
/
2011
In order to determine whether oxalate from grasses affects feed intake, blood calcium (Ca) and other blood parameters of adult sheep, two feeding trials were conducted. In Trial 1, one group of sheep received guineagrass (0.47% soluble oxalate) and another group received setaria (1.34% soluble oxalate) for 28 d. In Trial 2, one group of sheep received guineagrass while another group received the same grass treated with an oxalic acid solution (at a rate of 30 g oxalic acid/kg dry matter of hay) for 72 d. All sheep received concentrate mixtures (0.5% of body weight) throughout the experiment. In both trials, it was observed that plasma Ca concentration (11.0-11.7 mg/dl) was significantly (p<0.05) lower in sheep fed high oxalate-containing grasses than in sheep fed low oxalate-containing grasses (12.4-13.7 mg/dl). No differences (p>0.05) were observed in concentrations of magnesium, phosphorus and parathyroid hormone in plasma between the feeding of low and high oxalate-containing grasses. In addition, no differences (p>0.05) were observed in roughage dry mater (DM) intake, total DM intake or body weight of sheep. This study suggests that sheep may consume oxalate-rich forage, but Ca bioavailability may decrease with increasing oxalate levels in the ration.
$Amino-{\beta}-lactam$ antibiotics are absorbed by the dipeptide transporter in the small intestine. These uptakes are coupled to a proton influx. The inward proton gradient is partly induced by the $Na^+/H^+$ exchanger and calcium ion is involved in control of this antiport. Interaction between ampicillin which is one of the $Amino-{\beta}-lactam$ antibiotics and nifedipine which is one of calcium channel blocking agents was studied in rats in vivo and with rabbit jejunum mounted on the Sweetana/Grass diffusion cells in vitro. Bioavailability of ampicillin was increased significantly when nifedipine was co-administered orally in rats. There were no differences in the distribution phase and the elimination phase when ampicillin was given either alone or with nifedipine intravenously. Conditions for in vitro experiments were determined. The lift rate of $O_2/CO_2$ gas was controlled to 3 bubbles/sec and ampicillin was stable in the Kreb's buffer at pH 6.0. Absorption of ampicillin was the greatest when the completely-stripped serosal membrane was used. Transport of ampicillin from mucosal to serosal side in the rabbit jejunum was enhanced by 32% in the presence of nifedipine (p=0.059). Above results suggest that nifedipine might increase the plasma level of ampicillin via the improved absorption in the intestine rather than the reduction in the elimination or/and alteration in the distribution.
Irfan, Muhammad;Lee, Yuan Yee;Lee, Ki-Ja;Kim, Sung Dae;Rhee, Man Hee
Journal of Ginseng Research
/
v.46
no.3
/
pp.387-395
/
2022
Background: Fermentation may alter the bioavailability of certain compounds, which may affect their efficacy and pharmacological responses. This study investigated the antiplatelet effects of red ginseng extract (RGE) and fermented red ginseng extract (FRG). Methods: A rodent model was used to evaluate the antiplatelet and antithrombotic effects of the extracts. Rats were orally fed with human equivalent doses of the extracts for 1 week and examined for various signaling pathways using standard in vivo and ex vivo techniques. Light transmission aggregometry was performed, and calcium mobilization, dense granule secretion, integrin αIIbβ3-mediated signaling molecules, cyclic nucleotide signaling events, and various protein molecules were evaluated ex vivo in collagen-stimulated washed platelets. Furthermore, antithrombotic properties were evaluated using a standard acute pulmonary thromboembolism model, and the effects on hemostasis were investigated using rat and mice models. Results: Both RGE and FRG significantly inhibited platelet aggregation, calcium mobilization, and dense granule secretion along with integrin-mediated fibrinogen binding and fibrinogen adhesion. cAMP levels were found to be elevated in RGE-treated rat platelets. Ginseng extracts did not exert any effect on prothrombin time and activated partial thromboplastin time. RGE-treated mice showed significantly better survival under thrombosis than FRG-treated mice, with no effects on hemostasis, whereas FRG-treated mice exhibited a slight increment in bleeding time. Conclusion: Both extracts, especially RGE, are remarkable supplements to maintain cardiovascular health and are potential candidates for the treatment and prevention of platelet-related cardiovascular disorders.
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