薬理と治療
Volume 36, Issue 6, 2008
Volumes & issues:
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ORIGINAL ARTICLES
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抗てんかん薬トピラマートのラット単回経口投与時の分布,胎児移行および乳汁移行
36巻6号(2008);View Description Hide DescriptionObjectives To study the tissue distribution and transfer into the fetus or milk of topiramate in rats. Methods [14C]−topiramate was orally administered to male rats, and pregnant and lactating female rats at a dose of 40 mg/kg. Then, blood, tissues, fetus, and milk were collected and analyzed for radioactivity. Results Tissue concentrations of radioactivity in male rats showed the maximum levels in most tissues at 0.5 hours after administration. The concentration in the brain was 40−50% of that in plasma up to 4 hours after administration, while the levels in other tissues were lower than or equal to the level in plasma. Radioactivity levels decreased to 1.4% or lower of the maximum levels in all tissues at 72 hours. After administration to pregnant rats on the 19th day of gestation, radioactivity was transferred into the fetus. The concentration in the fetus was close to that in maternal plasma and decreased in parallel with the maternal plasma level. The concentration in milk reached the maximum level(24.32μg eq./g)1.40 hours after administration to lactating rats on the 9th day after delivery, which levels decreasing faster than what was observed in plasma. The milk/plasma concentration ratio was 0.07−0.73 and decreased with time. Conclusions Topiramate was distributed into most tissues including the brain and transferred to the fetus and milk in rats. However, the elimination rate of concentrations in tissues, fetus and milk was faster than or equal to that in plasma. These data suggested topiramate did not remain in the body over a long period. (Jpn Pharmacol Ther 2008;36:493−9) KEY WORDS Topiramate, Distribution, Pregnancy, Milk, Pharmacokinetics -
機能性食品の市販後調査研究
36巻6号(2008);View Description Hide DescriptionOsaka Association of General Physician established the“Osaka Life−style Related Diseases Prevention Network” to investigate the efficacy and safety of functional foods in patients. We have currently focused on constipation, which is general disorder in clinical practice, and conducted a study. The subjects were 132 men and women aged 20 to 70 years with constipation and abdominal disorder. The subjects were instructed to take a commercially available yogurt including Bifidobacterium lactis DN−173 010 for approximately 2 weeks and the states of constipation and abdominal disorder before and after consumption were investigated. The results revealed that there were greater improvements including increased stool frequency and softness and decreased abdominal pain and discomfort after consumption than before consumption. For the safety, 3 adverse events that could be related to the test food occurred in 3 out of 117 subjects who were analyzed for safety. All of these events were minimal and were less likely to be related to the test food. There was no interaction with specific drugs. These results indicate that the yogurt containing B. lactis DN−173 010 was effective in patients with constipation and abdominal disorder, has high safety in combination with pharmaceutical agents, and is useful in clinical practice. (Jpn Pharmacol Ther 2008;36:501−7)KEY WORDS Bifidobacterium lactis DN−173 010, Constipation, Abdominal pain and discomfort -
高濃度茶カテキンの継続摂取による内臓脂肪低減およびメタボリックシンドロームに及ぼす影響
36巻6号(2008);View Description Hide DescriptionBackground Long−term ingestion of high dose green tea catechins was reported to reduce visceral fat accumulation in several clinical studies. Objective This pooling−analysis was conducted to more precisely define the effect of high dose green tea catechins on visceral fat and metabolic syndrome. Methods The 7 studies in the pooling−analysis included a total 902 subjects receiving green tea catechins or placebo drinks. All studies evaluated visceral fat area by computer tomography after 8−12 weeks test period. The metabolic syndrome was diagnosed according to the definition for the Japanese. Results Ingestion of 539.7−587.5 mg/d green tea catechins for 8−12 weeks reduced visceral fat area, waist circumference and BMI. Blood pressure was also lowered especially in the subject with high blood pressure. Subject with metabolic syndrome at the baseline was significantly improved in high dose catechin group as compared to low dose group. Conclusion Ingestion of high−dose green tea catechins reduced visceral fat accumulation and improved metabolic syndrome.(Jpn Pharmacol Ther 2008;36:509−14)KEY WORDS Green tea catechins, Visceral fat, Metabolic syndrome, Pooling−analysis -
米ペプチドの正常高値および軽症・中等症高血圧者に対する長期摂取時の有効性および安全性
36巻6号(2008);View Description Hide DescriptionSake lees are obtained as a by−product in a manufacturing process of the liquor made from rice. It’s confirmed that several peptides obtained by treatment of sake lees with protease have an angiotensinI−converting enzyme inhibitor(ACE−I)activity. We investigated the hypotensive effects and safety of rice peptide in a placebo controlled single−blind study. 38 volunteers(male/female=21/17)with high−normal blood pressure, mild hypertension or moderate hypertension untreated with drugs. The rice peptide group(male/female=11/8, mean age 51 years, SBP/DBP=148.9±16.0 mmHg/92.9±7.8 mmHg)was given the test capsule containing 600 mg rice peptide(1000 mg as a material), and the control group(male/female=10/9, mean age 48 years, SBP/DBP=143.4±11.5 mmHg/92.1±7.9 mmHg) was given the placebo capsule, over a period of 12 weeks. The results revealed that the SBP was significantly reduced at 4, 8, 12 weeks(SBP/DBP=140.8±14.7 mmHg/88.2±10.1 mmHg)in the rice peptide group, but it was not significantly lower versus placebo group. And the pulse wave velocity(PWV)was a significant fluctuation to 1499.2±266.8(cm/s)from 1562.0±340.5(cm/s)in the rice peptide group. In addition, no adverse event and no marked changes were observed in pulse rate, blood indexes, urinalysis, and physical examination. These results suggest that the rice peptide moderately reduces the blood pressure in subjects with high−normal blood pressure, mild hypertension or moderate hypertension and that it is also very safe.(Jpn Pharmacol Ther 2008;36:517−29)KEY WORDS Rice peptide, Hypertension, PWV(pulse wave velocity), ACE−I -
Globin Digest Suppresses Postprandial Elevation of Remnant−like Particles by Activation of Lipoprotein Lipase and Hepatic Triglyceride Lipase
36巻6号(2008);View Description Hide DescriptionGlobin digest(GD)that produced from enzymatic hydrolysis of globin protein in hemoglobin suppressed postprandial elevations of chylomicron triglycerides in man. High lipoprotein remnant level after fat ingestion is a risk factor for atherosclerosis. Effect of GD was studied on postprandial remnant−like particles(RLP)as an index of lipoprotein remnant and on lipoprotein lipase(LPL)and hepatic triglyceride lipase(HTGL)activities. Twelve healthy subjects attended to a placebo−controlled crossover study. The subjects ingested a control high fat diet with or without GD. The increases of RLP concentration after ingestion of GD 1 g were significantly lower than the control. The areas under the curves of RLP during 6h of GD group were 30−50% lower than the corresponding control group. Another placebo−controlled crossover trial was performed using the same diet to examine the influence of GD on LPL and HTGL activities in the healthy participants. The LPL and HTGL in the subjects were activated by GD supplementation. Activation of the lipases by GD was indirect action through inner activators. When the subjects ingested GD 3 g, serum insulin levels temporary increased than the control. The activation of lipases seemed to occur through insulin’s action. Pancreatic lipase activities were reduced dose−dependently by GD in vitro. Suppression of pancreatic lipase and activation of LPL and HTGL by GD might be contributed to the reduction of postprandial RLP levels. GD seems to be useful for lowering incidence of cardiovascular diseases and atherosclerosis.(Jpn Pharmacol Ther 2008;36:531−40)KEY WORDS Globin digest, Remnant−like particles, Lipoprotein lipase, Hepatic triglyceride lipase, Insulin -
マンノオリゴ糖配合ミルク入り液体コーヒーの摂取が体脂肪低減に及ぼす影響
36巻6号(2008);View Description Hide DescriptionTest drinks termed“milk added liquid coffee”containing mannooligosaccharides from coffee mannan were administered to 48 healthy volunteers, and the effect on body fat reduction was investigated. Volunteers were divided into two groups for a placebo controlled double blind parallel test. Milk added liquid coffee(275 g)containing 3.0 g mannooligosaccharides or dextrin(as the placebo)was consumed each day by volunteers for 16 weeks. Physical examination was accompanied by measurements of blood indices, abdominal fat area as determined by computed tomography(CT)scan, and total body fat as determined by dual energy X−ray absorptiometry(DEXA). Abdominal total fat area in the test group was significantly reduced compared with the same subjects before administration and with the placebo group(both p<0.001). Furthermore, waist size, arm skinfold thickness, back skinfold thickness and total body fat mass in the test group showed a significant reduction over the 16 week period(p<0.001, p<0.01, p<0.001 and p<0.05, respectively). These results suggest that milk added liquid coffee containing mannooligosaccharides reduces human abdominal fat. (Jpn Pharmacol Ther 2008;36:541−8)KEY WORDS Mannooligosaccharides, Milk added liquid coffee, Abdominal fat area, Total body fat mass -
鶏コラーゲン加水分解物(C−COP)を配合した乳酸菌飲料の過剰摂取時における安全性
36巻6号(2008);View Description Hide DescriptionObjectives Chicken collagen hydrolysate(Chicken−Collagen Octa Peptides;C−COP)contains a peptide(Gly−Ala−Hyp−Gly−Leu−Hyp−Gly−Pro)with angiotensin converting enzyme (ACE)−inhibitory activity. Four weeks of C−COP administration at 2.9 g/day has already been found to reduce blood pressure in humans. Here, we investigate the safety of excess administration of lactic acid beverage containing C−COP. Methods A total of 48 subjects with mild hypertension or high−normal blood pressure were randomly assigned to two treatment groups:a test−food group in which subjects were given a lactic acid drink containing three times(8.7 g/day)the amount of C−COP usually given(2.9g/day), and a placebo group in which subjects were given a dummy drink. The study period comprised a total of 6 weeks:4 weeks of treatment and a 2−week post−treatment observation period to investigate the parameters related to safety. Results No clinically meaningful adverse effects or abnormal changes in laboratory results due to intake of lactic acid beverage containing C−COP were observed. In addition, no subjects showed dramatic reductions in blood pressure or any hypotensive symptoms. Conclusions These results suggest that the lactic acid beverage containing C−COP has a high safety profile, even in the case of excess administration. (Jpn Pharmacol Ther 2008;36:549−59)KEY WORDS C−COP(Chicken−Collagen Octa Peptides), ACE−inhibitory activity, Excess administration, Safety -
鶏コラーゲン加水分解物(C−COP)を配合した乳酸菌飲料による軽症高血圧者および正常高値血圧者に対する降圧作用と安全性の検討
36巻6号(2008);View Description Hide DescriptionObjectives Chicken collagen hydrolysate(Chicken−Collagen Octa Peptides;C−COP)contains a peptide(Gly−Ala−Hyp−Gly−Leu−Hyp−Gly−Pro)with an inhibitory effect of angiotensin converting enzyme(ACE). Four weeks of C−COP administration at 2.9 g/day has already been found to reduce blood pressure in humans. Here, we investigated both efficacy and safety of a long−term administration(12 weeks)of a lactic acid beverage containing C−COP. Methods A total of 120 subjects with either mild hypertension or high−normal blood pressure were randomly assigned to 2 groups:a test−food group in which subjects were given a lactic acid drink containing C−COP at 2.9 g/day, and a placebo group in which subjects were given a dummy drink. The study period comprised a total of 18 weeks:2 observational weeks before the treatment, a 12−week treatment period, and 4 weeks for the post−treatment observation to investigate the parameters related to hypotensive effects and safety. Results Systolic blood pressure in the test−food group was significantly reduced compared with that in the placebo group. In addition, when compared with the baseline values, blood pressure was continuously reduced from 2 weeks after onset of administration in the test food group. No clinically meaningful adverse effects or abnormal changes in laboratory results were observed.Conclusion These results suggest that the lactic acid beverage containing C−COP is a useful food because it safely reduced blood pressure in subjects with mild hypertension or highnormal blood pressure.(Jpn Pharmacol Ther 2008;36:561−75)KEY WORDS C−COP(Chicken−Collagen Octa Peptides), ACE−inhibitory activity, Longterm administration, Safety
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