The Experts below are selected from a list of 672 Experts worldwide ranked by ideXlab platform
Jun Iwamoto - One of the best experts on this subject based on the ideXlab platform.
-
Vitamin K 2 Therapy for Postmenopausal Osteoporosis
2020Co-Authors: Jun IwamotoAbstract:Abstract: Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K 2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of Menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of Menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that Menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and Menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of Menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of Menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.
-
Strategy for Prevention of Hip Fractures in Patients with Alzheimer's
2020Co-Authors: Jun Iwamoto, Yoshihiro SatoAbstract:The incidence of fractures, particularly hip fractures, is known to be high in patients with Alzheimer’s disease. The aim of this review was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer’s disease. The literature was searched using PubMed for randomized controlled trials (RCTs) regarding Alzheimer’s disease and hip fractures. Four RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for the individual RCTs. Sunlight exposure increased the serum level of 25-hydroxyvitamin D, promoted muscle strength, and prevented falls. Menatetrenone (vitamin K2) with vitamin D supplementation decreased the serum level of undercarboxylated osteocalcin. Risedronate with vitamin D supplementation decreased the urinary level of deoxypyridinoline. Sunlight exposure, Menatetrenone, and risedronate reduced the incidence of hip fractures, with RR (95% CI) of 0.22 (0.049, 0.999), 0.13 (0.031, 0.554), and 0.28 (0.105, 0.732), respectively. Combined treatment with risedronate and Menatetrenone was more effective in preventing hip fractures than single treatment with risedronate, with RR (95% CI) of 0.19 (0.044, 0.858). However, the quality of RCTs was the highest in two risedronate studies which adopted a placebo control group. The present review of the literature implies that sunlight exposure, Menatetrenone, and risedronate act on the musculoskeletal system in different manners for preventing hip fractures in patients with Alzheimer’s disease. However, risedronate plus vitamin D supplementation or risedronate plus Menatetrenone can be candidates in patients with Alzheimer’s disease.
-
Prevention of hip fractures by exposure to sunlight and pharmacotherapy in patients with Alzheimer's disease.
Aging clinical and experimental research, 2020Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro Sato, Kiyoshi Tanaka, Hideo MatsumotoAbstract:Hypovitaminosis D and K due to malnutrition or sunlight deprivation, compensatory hyperparathyroidism, increased bone resorption, low bone mineral density (BMD), and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Alzheimer's disease. The purpose of the present study was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer's disease. With respect to randomized controlled trials (RCTs) regarding Alzheimer's disease and hip fractures, the literature was searched with PubMed. Three RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for individual RCTs. Exposure to sunlight with calcium supplementation, Menatetrenone (vitamin K2) plus calcium and vitamin D supplementation, and risedronate plus calcium and vitamin D supplementation improved hypovitaminosis D and hyperparathyroidism, contributing to a reduction in bone resorption. Risedronate itself strongly decreased bone resorption. Menatetrenone also decreased the serum level of undercarboxylated osteocalcin. The three interventions increased metacarpal BMD and reduced the incidence of hip fractures. The respective RRs (95% CI) were 0.22 (0.049-0.999), 0.13 (0.031-0.554), and 0.26 (0.100- 0.690). The present study clarified the efficacy of three interventions, including exposure to sunlight, Menatetrenone, and risedronate with calcium and/or vitamin D supplementation against hip fractures in patients with Alzheimer's disease.
-
Treatment with vitamin D 3 and/or vitamin K 2 for postmenopausal osteoporosis
2020Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Shoichi IchimuraAbstract:It is established in Japan that treatment with 1a-hydroxyvitamin D3 (alfacalcidol) slightly reduces bone turnover, sustains lumbar bone mineral density (BMD), and prevents osteoporotic vertebral fractures in postmenopausal women with osteoporosis, while vitamin K2 (Menatetrenone) enhances g-carboxylation of bone glutamic acid residues and secretion of osteocalcin, sustains lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Available evidence suggests that the effect of vitamin K2 on mineralization by human periosteal osteoblasts is enhanced in the presence of 1,25 dihydroxyvitamin D3 in vitro. The effect of vitamin K2 on BMD in ovariectomized rats is affected by the plasma 25-hydroxyvitamin D3 level in vivo, and is significant only when rats are fed a diet containing vitamin D3. Based on this line of evidence, combined treatment with alfacalcidol and Menatetrenone for osteoporosis is surmised to be more effective than treatment with Menatetrenone alone, and may have anabolic effects on osteoporotic bone. This combined treatment may increase bone formation as well as bone resorption over the mild anti-resorptive effect of alfacalcidol itself, and shows the greatest effect on lumbar BMD or the incidence of vertebral fractures in studies in which the mean age and years since menopause of subjects were low and the degree of osteoporosis was mild. It may be effective for mild postmenopausal osteoporosis in which age-related deterioration of tra- becular bone properties remains below the threshold for vertebral fractures, even if bone resorption is increased and trabecular bone has deteriorated. (Keio J Med 52 (3): 147-150, September 2003)
-
retraction note to efficacy of Menatetrenone vitamin k2 against non vertebral and hip fractures in patients with neurological diseases meta analysis of three randomized controlled trials
Clinical Drug Investigation, 2018Co-Authors: Jun Iwamoto, Hideo Matsumoto, Tsuyoshi TakedaAbstract:Background and objective: Patients with neurological diseases such as Alzheimer’s disease, stroke and Parkinson’s disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of Menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases.
Seigo Iwakawa - One of the best experts on this subject based on the ideXlab platform.
-
Effect of oxyethylene moiety in polyoxyethylene sorbitan esters on the pharmacokinetics of Menatetrenone incorporated in O/W lipid emulsions prepared with polyoxyethylene sorbitan esters and soybean oil in rats.
Journal of Pharmacy and Pharmacology, 2020Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Yuriko Kawaguchi, Seigo IwakawaAbstract:: Oil-in-water (O/W) lipid emulsions are suitable drug carriers for lipophilic drugs; however, the effects of numbers or chains of oxyethylene units within a surfactant molecule such as polyoxyethylene sorbitan esters (PSs) on the biological fate of these lipid emulsions have not yet been clarified. In this study, a series of PSs and soybean oil (SO) were utilized to prepare Menatetrenone-incorporated lipid emulsions (SO/PSs), and the biological fate of Menatetrenone administered as SO/PSs was studied at a clinical injection volume (0.1 mL kg(-1)) in rats. The plasma concentration and organ uptake of Menatetrenone administered as SO/20OE-PSs (PSs with 20 oxyethylene units) was similar to that of SO/egg-yolk phosphatides (SO/EYP). The plasma concentration of Menatetrenone was extensively lower for SO/6OE-PSs (PSs with 6 oxyethylene units) and SO/20OE-3FA-PSs (PSs with 20 oxyethylene units and 3 fatty acid chains) than that for SO/EYP, and Menatetrenone uptake by the liver and spleen was higher for SO/6OE-PSs and SO/20OE-3FA-PSs, respectively, than those for SO/EYP. Furthermore, Menatetrenone uptake by the lungs was also increased for SO/6OE-PS and SO/20OE-3FA-PS with double bonds in the fatty acid moieties of the PSs. These findings suggested that shortening the oxyethylene units or decreasing the oxyethylene chain numbers of emulsifiers resulted in a rapid clearance of the lipid emulsions from the circulation by extensive uptake via the liver, spleen or lungs.
-
effect of oxyethylene numbers on the pharmacokinetics of Menatetrenone incorporated in oil in water lipid emulsions prepared with polyoxyethylene polyoxypropylene block copolymers and soybean oil in rats
Biological & Pharmaceutical Bulletin, 2008Co-Authors: Kumiko Ueda, Yuriko Kawaguchi, Seigo IwakawaAbstract:We have prepared lipid emulsions of approximately 200 nm in diameter with soybean oil (SO) and a series of Pluronics with various numbers of oxyethylene units and about 60 oxypropylene units (SO/Pluronics), and studied the pharmacokinetics of Menatetrenone incorporated into SO/Pluronics in rats. Emulsions of approximately 200 nm in diameter were obtained when SO contents were 2.5% and 20% (w/w) for 2.4% (w/w) PL101 and Pluronics that more than 30% was made up by oxyethylene units, respectively. The half-life of Menatetrenone in plasma when oxyethylene units made up less than 30% of the Pluronic (SO/PL101 and SO/PP103) was similar to that for SO/egg yolk phosphatides (SO/EYP), but longer than that when oxyethylene units composed more than 40% of the Pluronic (SO/PP104 and SO/PF108, by 3- and 10-fold, respectively). Pretreatment with dextran sulfate 500000, an inhibitor of emulsion uptake by the reticuloendothelial system (RES), resulted in a higher plasma concentration and a lower liver uptake of Menatetrenone as SO/PL101 at 10 min and SO/PP103 at 60 min, indicating that both SO/PL101 and SO/PP103 were taken up by the RES, although SO/PP103 required some time to be recognized by the RES. These findings suggested that larger numbers of oxyethylene units of Pluronics with 60 oxypropylene units were required for the longer plasma circulation of SO/Pluronics due to evasion of the RES.
-
effect of acyl chains of phosphatidylcholines on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with phosphatidylcholines and soybean oil in rats
Journal of Pharmacy and Pharmacology, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Seigo IwakawaAbstract:Oil-in-water (O/W) lipid emulsions were prepared with phosphatidylcholines (PCs) of various acyl chains and soybean oil (SO) using a microfluidizer system, and the pharmacokinetics of Menatetrenone incorporated in these oil particles were examined at the clinical injection volume (0.1 mL kg - 1 ) in rats. The plasma half-life of Menatetrenone incorporated in the oil particles prepared with SO and dipalmitoylphosphatidylcholine (DPPC) (SO/DPPC) was longer than that prepared with SO and egg-yolk phosphatides (EYP) (SO/EYP) by 3 fold, while those of Menatetrenone as oil particles prepared with SO and either dilauroyl phosphatidylcholine (DLPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DOPC) or dilinoleoyl phosphatidylcholine (DLoPC) (SO/DLPC, SO/DMPC, SO/DSPC, SO/DOPC and SO/DLoPC, respectively) were similar to that of Menatetrenone as SO/EYP. The Menatetrenone uptake by the liver was not significantly different from that as SO/EYP in all SO/PCs examined, but the Menatetrenone uptake by the spleen as SO/DPPC and SO/DSPC was higher than that as SO/EYP. The Menatetrenone uptake by the lungs as SO/DPPC was also higher than that as SO/EYP. These findings suggest that SO/DPPC is a good candidate drug carrier for the prolonged plasma circulation of lipophilic drugs.
-
prolonged circulation of Menatetrenone by emulsions with hydrogenated castor oils in rats
Journal of Controlled Release, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuriko Kawaguchi, Takashi Furukawa, Yosuke Miki, Seigo IwakawaAbstract:Abstract Previously, we reported that plasma half-lives of a drug incorporated in lipid emulsions prepared with soybean oil (SO), a long-chain triglyceride, and hydrogenated castor oils (HCOs) (SO/HCOs) were markedly longer, while those as SO/polyoxyethylene sorbitan esters (SO/PSs) were similar, compared to that as SO/egg yolk phosphatides (SO/EYP) [J. Pharm. Pharmacol. 54 (2002) 1357; J. Drug Target. 11 (2003) 37]. In the present study, lipid emulsions were prepared with Miglyol 812 (MO), a medium-chain triglyceride, and HCOs, and the kinetics of the incorporated drug, Menatetrenone, were examined. The plasma half-lives and the liver uptake of Menatetrenone as MO/polyoxyethylene-(10)-hydrogenated castor oils (MO/HCO10s) were similar to and larger than those as MO/EYP, respectively. On the other hand, the plasma half-lives and liver uptake of Menatetrenone as MO/polyoxyethylene-(20)-hydrogenated castor oils (MO/HCO20s) or MO/polyoxyethylene-(60)-hydrogenated castor oils (MO/HCO60s) were markedly longer and lower than those as MO/EYP, respectively. The pretreatment of dextran sulfate 500,000, a reticuloendothelial system suppressor, raised the plasma concentration and inhibited liver uptake of Menatetrenone as MO/HCO10, but not for MO/HCO20. These findings suggest that the minimum number of oxyethylene units within HCOs for the prolonged plasma circulation of Menatetrenone was 20 for MO/HCOs, similarly to SO/HCOs.
-
effect of oxyethylene moieties in hydrogenated castor oil on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with hydrogenated castor oil and soybean oil in rats
Journal of Drug Targeting, 2003Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuka Yamazaki, Hiromi Noto, Yasuko Teshima, Chiharu Yamashita, Seigo IwakawaAbstract:Lipid emulsions with particle sizes of 190–270 nm were prepared with soybean oil (SO) and a series of hydrogenated castor oils (HCOs) with various oxyethylene numbers, and the effect of oxyethylene numbers of HCOs on the pharmacokinetics of Menatetrenone incorporated into the lipid emulsions was studied in rats. Plasma half-life of Menatetrenone after administration as the lipid emulsions prepared by HCO with 10 oxyethylene units (SO/HCO10) was similar to that after the administration as SO/egg yolk phosphatides (SO/EYP), but was shorter than that as the lipid emulsions prepared by HCOs with >20 oxyethylene units (SO/HCO20, SO/HCO30, SO/HCO60 and SO/HCO100). Menatetrenone incorporated in SO/HCO10, SO/HCO20 and SO/HCO60 was not taken up by the blood cells in vitro, and the plasma level of Menatetrenone incorporated in SO/HCO10 was similar to that of triglycerides, suggesting that Menatetrenone was not released from the oil particles even after entering the circulation. Menatetrenone uptake by the liver for...
Yoshihiro Sato - One of the best experts on this subject based on the ideXlab platform.
-
Strategy for Prevention of Hip Fractures in Patients with Alzheimer's
2020Co-Authors: Jun Iwamoto, Yoshihiro SatoAbstract:The incidence of fractures, particularly hip fractures, is known to be high in patients with Alzheimer’s disease. The aim of this review was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer’s disease. The literature was searched using PubMed for randomized controlled trials (RCTs) regarding Alzheimer’s disease and hip fractures. Four RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for the individual RCTs. Sunlight exposure increased the serum level of 25-hydroxyvitamin D, promoted muscle strength, and prevented falls. Menatetrenone (vitamin K2) with vitamin D supplementation decreased the serum level of undercarboxylated osteocalcin. Risedronate with vitamin D supplementation decreased the urinary level of deoxypyridinoline. Sunlight exposure, Menatetrenone, and risedronate reduced the incidence of hip fractures, with RR (95% CI) of 0.22 (0.049, 0.999), 0.13 (0.031, 0.554), and 0.28 (0.105, 0.732), respectively. Combined treatment with risedronate and Menatetrenone was more effective in preventing hip fractures than single treatment with risedronate, with RR (95% CI) of 0.19 (0.044, 0.858). However, the quality of RCTs was the highest in two risedronate studies which adopted a placebo control group. The present review of the literature implies that sunlight exposure, Menatetrenone, and risedronate act on the musculoskeletal system in different manners for preventing hip fractures in patients with Alzheimer’s disease. However, risedronate plus vitamin D supplementation or risedronate plus Menatetrenone can be candidates in patients with Alzheimer’s disease.
-
Prevention of hip fractures by exposure to sunlight and pharmacotherapy in patients with Alzheimer's disease.
Aging clinical and experimental research, 2020Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro Sato, Kiyoshi Tanaka, Hideo MatsumotoAbstract:Hypovitaminosis D and K due to malnutrition or sunlight deprivation, compensatory hyperparathyroidism, increased bone resorption, low bone mineral density (BMD), and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Alzheimer's disease. The purpose of the present study was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer's disease. With respect to randomized controlled trials (RCTs) regarding Alzheimer's disease and hip fractures, the literature was searched with PubMed. Three RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for individual RCTs. Exposure to sunlight with calcium supplementation, Menatetrenone (vitamin K2) plus calcium and vitamin D supplementation, and risedronate plus calcium and vitamin D supplementation improved hypovitaminosis D and hyperparathyroidism, contributing to a reduction in bone resorption. Risedronate itself strongly decreased bone resorption. Menatetrenone also decreased the serum level of undercarboxylated osteocalcin. The three interventions increased metacarpal BMD and reduced the incidence of hip fractures. The respective RRs (95% CI) were 0.22 (0.049-0.999), 0.13 (0.031-0.554), and 0.26 (0.100- 0.690). The present study clarified the efficacy of three interventions, including exposure to sunlight, Menatetrenone, and risedronate with calcium and/or vitamin D supplementation against hip fractures in patients with Alzheimer's disease.
-
Strategy for Prevention of Hip Fractures in Patients with Alzheimer's Disease
2013Co-Authors: Jun Iwamoto, Yoshihiro SatoAbstract:The incidence of fractures, particularly hip fractures, is known to be high in patients with Alzheimer’s disease. The aim of this review was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer’s disease. The literature was searched using PubMed for randomized controlled trials (RCTs) regarding Alzheimer’s disease and hip fractures. Four RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for the individual RCTs. Sunlight exposure increased the serum level of 25-hydroxyvitamin D, promoted muscle strength, and prevented falls. Menatetrenone (vitamin K2) with vitamin D supplementation decreased the serum level of undercarboxylated osteocalcin. Risedronate with vitamin D supplementation decreased the urinary level of deoxypyridinoline. Sunlight exposure, Menatetrenone, and risedronate reduced the incidence of hip fractures, with RR (95% CI) of 0.22 (0.049, 0.999), 0.13 (0.031, 0.554), and 0.28 (0.105, 0.732), respectively. Combined treatment with risedronate and Menatetrenone was more effective in preventing hip fractures than single treatment with risedronate, with RR (95% CI) of 0.19 (0.044, 0.858). However, the quality of RCTs was the highest in two risedronate studies which adopted a placebo control group. The present review of the literature implies that sunlight exposure, Menatetrenone, and risedronate act on the musculoskeletal system in different manners for preventing hip fractures in patients with Alzheimer’s disease. However, risedronate plus vitamin D supplementation or risedronate plus Menatetrenone can be candidates in patients with Alzheimer’s disease.
-
Prevention of hip fractures by exposure to sunlight and pharmacotherapy in patients with Alzheimer's disease.
Aging Clinical and Experimental Research, 2013Co-Authors: Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro Sato, Kiyoshi Tanaka, Hideo MatsumotoAbstract:Background and aims: Hypovitaminosis D and K due to malnutrition or sunlight deprivation, compensatory hyperparathyroidism, increased bone resorption, low bone mineral density (BMD), and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Alzheimer’s disease. The purpose of the present study was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer’s disease. Methods: With respect to randomized controlled trials (RCTs) regarding Alzheimer’s disease and hip fractures, the literature was searched with PubMed. Results: Three RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for individual RCTs. Exposure to sunlight with calcium supplementation, Menatetrenone (vitamin K2) plus calcium and vitamin D supplementation, and risedronate plus calcium and vitamin D supplementation improved hypovitaminosis D and hyperparathyroidism, contributing to a reduction in bone resorption. Risedronate itself strongly decreased bone resorption. Menatetrenone also decreased the serum level of undercarboxylated osteocalcin. The three interventions increased metacarpal BMD and reduced the incidence of hip fractures. The respective RRs (95% CI) were 0.22 (0.049–0.999), 0.13 (0.031–0.554), and 0.26 (0.100–0.690). Conclusions: The present study clarified the efficacy of three interventions, including exposure to sunlight, Menatetrenone, and risedronate with calcium and/or vitamin D supplementation against hip fractures in patients with Alzheimer’s disease.
-
Menatetrenone for the treatment of osteoporosis
Expert Opinion on Pharmacotherapy, 2013Co-Authors: Jun Iwamoto, Yoshihiro SatoAbstract:Introduction: The effect of the anti-osteoporosis medicine, Menatetrenone (vitamin K2; menaquinone-4) on the skeleton remains a matter of controversy. The objective of the present review study was to evaluate the effect of Menatetrenone on the skeleton of postmenopausal women, men and glucocorticoid-treated patients. Methods: PubMed was used to search the literature for randomized controlled trials (RCTs), meta-analyses and systematic reviews. Thirteen RCTs, one meta-analysis and one systematic review were available for analysis. Results: Except for one large Japanese RCT (Phase IV trial: Osteoporotic Fracture (OF) study, n = 4378), RCTs with small sample size showed non-significant or modest effect on bone mineral density (BMD) in postmenopausal women and patients treated with glucocorticoid, positive effect on hip geometry in postmenopausal women and efficacy against fractures (mainly vertebral fractures) in postmenopausal women with osteoporosis. A post hoc analysis of the OF study showed that the inci...
Kumiko Ueda - One of the best experts on this subject based on the ideXlab platform.
-
Effect of oxyethylene moiety in polyoxyethylene sorbitan esters on the pharmacokinetics of Menatetrenone incorporated in O/W lipid emulsions prepared with polyoxyethylene sorbitan esters and soybean oil in rats.
Journal of Pharmacy and Pharmacology, 2020Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Yuriko Kawaguchi, Seigo IwakawaAbstract:: Oil-in-water (O/W) lipid emulsions are suitable drug carriers for lipophilic drugs; however, the effects of numbers or chains of oxyethylene units within a surfactant molecule such as polyoxyethylene sorbitan esters (PSs) on the biological fate of these lipid emulsions have not yet been clarified. In this study, a series of PSs and soybean oil (SO) were utilized to prepare Menatetrenone-incorporated lipid emulsions (SO/PSs), and the biological fate of Menatetrenone administered as SO/PSs was studied at a clinical injection volume (0.1 mL kg(-1)) in rats. The plasma concentration and organ uptake of Menatetrenone administered as SO/20OE-PSs (PSs with 20 oxyethylene units) was similar to that of SO/egg-yolk phosphatides (SO/EYP). The plasma concentration of Menatetrenone was extensively lower for SO/6OE-PSs (PSs with 6 oxyethylene units) and SO/20OE-3FA-PSs (PSs with 20 oxyethylene units and 3 fatty acid chains) than that for SO/EYP, and Menatetrenone uptake by the liver and spleen was higher for SO/6OE-PSs and SO/20OE-3FA-PSs, respectively, than those for SO/EYP. Furthermore, Menatetrenone uptake by the lungs was also increased for SO/6OE-PS and SO/20OE-3FA-PS with double bonds in the fatty acid moieties of the PSs. These findings suggested that shortening the oxyethylene units or decreasing the oxyethylene chain numbers of emulsifiers resulted in a rapid clearance of the lipid emulsions from the circulation by extensive uptake via the liver, spleen or lungs.
-
effect of oxyethylene numbers on the pharmacokinetics of Menatetrenone incorporated in oil in water lipid emulsions prepared with polyoxyethylene polyoxypropylene block copolymers and soybean oil in rats
Biological & Pharmaceutical Bulletin, 2008Co-Authors: Kumiko Ueda, Yuriko Kawaguchi, Seigo IwakawaAbstract:We have prepared lipid emulsions of approximately 200 nm in diameter with soybean oil (SO) and a series of Pluronics with various numbers of oxyethylene units and about 60 oxypropylene units (SO/Pluronics), and studied the pharmacokinetics of Menatetrenone incorporated into SO/Pluronics in rats. Emulsions of approximately 200 nm in diameter were obtained when SO contents were 2.5% and 20% (w/w) for 2.4% (w/w) PL101 and Pluronics that more than 30% was made up by oxyethylene units, respectively. The half-life of Menatetrenone in plasma when oxyethylene units made up less than 30% of the Pluronic (SO/PL101 and SO/PP103) was similar to that for SO/egg yolk phosphatides (SO/EYP), but longer than that when oxyethylene units composed more than 40% of the Pluronic (SO/PP104 and SO/PF108, by 3- and 10-fold, respectively). Pretreatment with dextran sulfate 500000, an inhibitor of emulsion uptake by the reticuloendothelial system (RES), resulted in a higher plasma concentration and a lower liver uptake of Menatetrenone as SO/PL101 at 10 min and SO/PP103 at 60 min, indicating that both SO/PL101 and SO/PP103 were taken up by the RES, although SO/PP103 required some time to be recognized by the RES. These findings suggested that larger numbers of oxyethylene units of Pluronics with 60 oxypropylene units were required for the longer plasma circulation of SO/Pluronics due to evasion of the RES.
-
effect of acyl chains of phosphatidylcholines on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with phosphatidylcholines and soybean oil in rats
Journal of Pharmacy and Pharmacology, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Seigo IwakawaAbstract:Oil-in-water (O/W) lipid emulsions were prepared with phosphatidylcholines (PCs) of various acyl chains and soybean oil (SO) using a microfluidizer system, and the pharmacokinetics of Menatetrenone incorporated in these oil particles were examined at the clinical injection volume (0.1 mL kg - 1 ) in rats. The plasma half-life of Menatetrenone incorporated in the oil particles prepared with SO and dipalmitoylphosphatidylcholine (DPPC) (SO/DPPC) was longer than that prepared with SO and egg-yolk phosphatides (EYP) (SO/EYP) by 3 fold, while those of Menatetrenone as oil particles prepared with SO and either dilauroyl phosphatidylcholine (DLPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DOPC) or dilinoleoyl phosphatidylcholine (DLoPC) (SO/DLPC, SO/DMPC, SO/DSPC, SO/DOPC and SO/DLoPC, respectively) were similar to that of Menatetrenone as SO/EYP. The Menatetrenone uptake by the liver was not significantly different from that as SO/EYP in all SO/PCs examined, but the Menatetrenone uptake by the spleen as SO/DPPC and SO/DSPC was higher than that as SO/EYP. The Menatetrenone uptake by the lungs as SO/DPPC was also higher than that as SO/EYP. These findings suggest that SO/DPPC is a good candidate drug carrier for the prolonged plasma circulation of lipophilic drugs.
-
prolonged circulation of Menatetrenone by emulsions with hydrogenated castor oils in rats
Journal of Controlled Release, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuriko Kawaguchi, Takashi Furukawa, Yosuke Miki, Seigo IwakawaAbstract:Abstract Previously, we reported that plasma half-lives of a drug incorporated in lipid emulsions prepared with soybean oil (SO), a long-chain triglyceride, and hydrogenated castor oils (HCOs) (SO/HCOs) were markedly longer, while those as SO/polyoxyethylene sorbitan esters (SO/PSs) were similar, compared to that as SO/egg yolk phosphatides (SO/EYP) [J. Pharm. Pharmacol. 54 (2002) 1357; J. Drug Target. 11 (2003) 37]. In the present study, lipid emulsions were prepared with Miglyol 812 (MO), a medium-chain triglyceride, and HCOs, and the kinetics of the incorporated drug, Menatetrenone, were examined. The plasma half-lives and the liver uptake of Menatetrenone as MO/polyoxyethylene-(10)-hydrogenated castor oils (MO/HCO10s) were similar to and larger than those as MO/EYP, respectively. On the other hand, the plasma half-lives and liver uptake of Menatetrenone as MO/polyoxyethylene-(20)-hydrogenated castor oils (MO/HCO20s) or MO/polyoxyethylene-(60)-hydrogenated castor oils (MO/HCO60s) were markedly longer and lower than those as MO/EYP, respectively. The pretreatment of dextran sulfate 500,000, a reticuloendothelial system suppressor, raised the plasma concentration and inhibited liver uptake of Menatetrenone as MO/HCO10, but not for MO/HCO20. These findings suggest that the minimum number of oxyethylene units within HCOs for the prolonged plasma circulation of Menatetrenone was 20 for MO/HCOs, similarly to SO/HCOs.
-
effect of oxyethylene moieties in hydrogenated castor oil on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with hydrogenated castor oil and soybean oil in rats
Journal of Drug Targeting, 2003Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuka Yamazaki, Hiromi Noto, Yasuko Teshima, Chiharu Yamashita, Seigo IwakawaAbstract:Lipid emulsions with particle sizes of 190–270 nm were prepared with soybean oil (SO) and a series of hydrogenated castor oils (HCOs) with various oxyethylene numbers, and the effect of oxyethylene numbers of HCOs on the pharmacokinetics of Menatetrenone incorporated into the lipid emulsions was studied in rats. Plasma half-life of Menatetrenone after administration as the lipid emulsions prepared by HCO with 10 oxyethylene units (SO/HCO10) was similar to that after the administration as SO/egg yolk phosphatides (SO/EYP), but was shorter than that as the lipid emulsions prepared by HCOs with >20 oxyethylene units (SO/HCO20, SO/HCO30, SO/HCO60 and SO/HCO100). Menatetrenone incorporated in SO/HCO10, SO/HCO20 and SO/HCO60 was not taken up by the blood cells in vitro, and the plasma level of Menatetrenone incorporated in SO/HCO10 was similar to that of triglycerides, suggesting that Menatetrenone was not released from the oil particles even after entering the circulation. Menatetrenone uptake by the liver for...
Toshiyuki Sakaeda - One of the best experts on this subject based on the ideXlab platform.
-
Effect of oxyethylene moiety in polyoxyethylene sorbitan esters on the pharmacokinetics of Menatetrenone incorporated in O/W lipid emulsions prepared with polyoxyethylene sorbitan esters and soybean oil in rats.
Journal of Pharmacy and Pharmacology, 2020Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Yuriko Kawaguchi, Seigo IwakawaAbstract:: Oil-in-water (O/W) lipid emulsions are suitable drug carriers for lipophilic drugs; however, the effects of numbers or chains of oxyethylene units within a surfactant molecule such as polyoxyethylene sorbitan esters (PSs) on the biological fate of these lipid emulsions have not yet been clarified. In this study, a series of PSs and soybean oil (SO) were utilized to prepare Menatetrenone-incorporated lipid emulsions (SO/PSs), and the biological fate of Menatetrenone administered as SO/PSs was studied at a clinical injection volume (0.1 mL kg(-1)) in rats. The plasma concentration and organ uptake of Menatetrenone administered as SO/20OE-PSs (PSs with 20 oxyethylene units) was similar to that of SO/egg-yolk phosphatides (SO/EYP). The plasma concentration of Menatetrenone was extensively lower for SO/6OE-PSs (PSs with 6 oxyethylene units) and SO/20OE-3FA-PSs (PSs with 20 oxyethylene units and 3 fatty acid chains) than that for SO/EYP, and Menatetrenone uptake by the liver and spleen was higher for SO/6OE-PSs and SO/20OE-3FA-PSs, respectively, than those for SO/EYP. Furthermore, Menatetrenone uptake by the lungs was also increased for SO/6OE-PS and SO/20OE-3FA-PS with double bonds in the fatty acid moieties of the PSs. These findings suggested that shortening the oxyethylene units or decreasing the oxyethylene chain numbers of emulsifiers resulted in a rapid clearance of the lipid emulsions from the circulation by extensive uptake via the liver, spleen or lungs.
-
O/W lipid emulsions for parenteral drug delivery. IV. Changes in the pharmacokinetics and pharmacodynamics of a highly lipophilic drug, Menatetrenone.
Journal of Drug Targeting, 2009Co-Authors: Toshiyuki Sakaeda, Hisato Kakushi, Tsutomu Shike, Kyoji Takano, Toshio Harauchi, Masaharu Hirata, Koichiro HiranoAbstract:AbstractThe pharmacokinetics and pharmacodynamics of antihemorrhagic vitamin, Menatetrenone after intravenous injection as the lipid emulsion, were compared to those as the micellar solutions. Menatetrenone was selectively delivered to the liver, lungs and spleen and retained in them. Hepatic and splenetic concentration at 6 h (C6h) increased 21.6- and 27.1-fold, respectively, and the area under the tissue concentration-time curve up to 6 h (AUC0-6h) were 2.3- and 11.4-fold, respectively, when compared with its micellar solution. Antihemorrhagic effect of Menatetrenone was assessed using warfarin-induced hypoprothrombinemic rats. The lipid emulsion of Menatetrenone decreased the prothrombin time at 6h after intravenous injection more effectively than micellar solution. The dose-response curves indicated that the efficacy of the lipid emulsion was 2.4-2.9 times that of a micellar solution, and this was correlated with AUC0-6h rather than C6h The plasma level of clotting factor VII and the hepatic level of ...
-
effect of acyl chains of phosphatidylcholines on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with phosphatidylcholines and soybean oil in rats
Journal of Pharmacy and Pharmacology, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Masanori Fujimoto, Hiromi Noto, Seigo IwakawaAbstract:Oil-in-water (O/W) lipid emulsions were prepared with phosphatidylcholines (PCs) of various acyl chains and soybean oil (SO) using a microfluidizer system, and the pharmacokinetics of Menatetrenone incorporated in these oil particles were examined at the clinical injection volume (0.1 mL kg - 1 ) in rats. The plasma half-life of Menatetrenone incorporated in the oil particles prepared with SO and dipalmitoylphosphatidylcholine (DPPC) (SO/DPPC) was longer than that prepared with SO and egg-yolk phosphatides (EYP) (SO/EYP) by 3 fold, while those of Menatetrenone as oil particles prepared with SO and either dilauroyl phosphatidylcholine (DLPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DOPC) or dilinoleoyl phosphatidylcholine (DLoPC) (SO/DLPC, SO/DMPC, SO/DSPC, SO/DOPC and SO/DLoPC, respectively) were similar to that of Menatetrenone as SO/EYP. The Menatetrenone uptake by the liver was not significantly different from that as SO/EYP in all SO/PCs examined, but the Menatetrenone uptake by the spleen as SO/DPPC and SO/DSPC was higher than that as SO/EYP. The Menatetrenone uptake by the lungs as SO/DPPC was also higher than that as SO/EYP. These findings suggest that SO/DPPC is a good candidate drug carrier for the prolonged plasma circulation of lipophilic drugs.
-
prolonged circulation of Menatetrenone by emulsions with hydrogenated castor oils in rats
Journal of Controlled Release, 2004Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuriko Kawaguchi, Takashi Furukawa, Yosuke Miki, Seigo IwakawaAbstract:Abstract Previously, we reported that plasma half-lives of a drug incorporated in lipid emulsions prepared with soybean oil (SO), a long-chain triglyceride, and hydrogenated castor oils (HCOs) (SO/HCOs) were markedly longer, while those as SO/polyoxyethylene sorbitan esters (SO/PSs) were similar, compared to that as SO/egg yolk phosphatides (SO/EYP) [J. Pharm. Pharmacol. 54 (2002) 1357; J. Drug Target. 11 (2003) 37]. In the present study, lipid emulsions were prepared with Miglyol 812 (MO), a medium-chain triglyceride, and HCOs, and the kinetics of the incorporated drug, Menatetrenone, were examined. The plasma half-lives and the liver uptake of Menatetrenone as MO/polyoxyethylene-(10)-hydrogenated castor oils (MO/HCO10s) were similar to and larger than those as MO/EYP, respectively. On the other hand, the plasma half-lives and liver uptake of Menatetrenone as MO/polyoxyethylene-(20)-hydrogenated castor oils (MO/HCO20s) or MO/polyoxyethylene-(60)-hydrogenated castor oils (MO/HCO60s) were markedly longer and lower than those as MO/EYP, respectively. The pretreatment of dextran sulfate 500,000, a reticuloendothelial system suppressor, raised the plasma concentration and inhibited liver uptake of Menatetrenone as MO/HCO10, but not for MO/HCO20. These findings suggest that the minimum number of oxyethylene units within HCOs for the prolonged plasma circulation of Menatetrenone was 20 for MO/HCOs, similarly to SO/HCOs.
-
effect of oxyethylene moieties in hydrogenated castor oil on the pharmacokinetics of Menatetrenone incorporated in o w lipid emulsions prepared with hydrogenated castor oil and soybean oil in rats
Journal of Drug Targeting, 2003Co-Authors: Kumiko Ueda, Toshiyuki Sakaeda, Yuka Yamazaki, Hiromi Noto, Yasuko Teshima, Chiharu Yamashita, Seigo IwakawaAbstract:Lipid emulsions with particle sizes of 190–270 nm were prepared with soybean oil (SO) and a series of hydrogenated castor oils (HCOs) with various oxyethylene numbers, and the effect of oxyethylene numbers of HCOs on the pharmacokinetics of Menatetrenone incorporated into the lipid emulsions was studied in rats. Plasma half-life of Menatetrenone after administration as the lipid emulsions prepared by HCO with 10 oxyethylene units (SO/HCO10) was similar to that after the administration as SO/egg yolk phosphatides (SO/EYP), but was shorter than that as the lipid emulsions prepared by HCOs with >20 oxyethylene units (SO/HCO20, SO/HCO30, SO/HCO60 and SO/HCO100). Menatetrenone incorporated in SO/HCO10, SO/HCO20 and SO/HCO60 was not taken up by the blood cells in vitro, and the plasma level of Menatetrenone incorporated in SO/HCO10 was similar to that of triglycerides, suggesting that Menatetrenone was not released from the oil particles even after entering the circulation. Menatetrenone uptake by the liver for...