薬理と治療
Volume 36, Issue 3, 2008
Volumes & issues:
-
TOPICS
-
-
「適応型デザインで計画された検証的臨床試験における方法論上の問題に関するReflection Paper」訳
36巻3号(2008);View Description Hide Description中間解析の結果にもとづいたデザイン変更を含む,いわゆる適応型デザイン(adaptive design)を用いて試験を計画することが可能な場合がある。そのようなデザインでは,薬剤開発のスピードアップを図れる可能性が生じたり,あるいは科学的もしくは規制上の基準を低下させることなく,より効率的な資源の割り当てに利用できたりすることが期待される。これは,もし同時に規制当局の意思決定の基礎を改善することができるならば,とくに歓迎すべきものである。しかしながら,臨床開発計画において,第III相の目的は,前臨床試験,忍容性試験,用量設定試験やその他の第II相試験からの知見を検証することである(CPMP/EWP/2330/99)。それゆえ,第III相試験(あるいは検証パッケージの一部と考えられる後期第II相試験)におけるデザイン修正を認めることは,そのような試験の検証的性格に矛盾することになり,よりいっそうの正当な理由なしには受け入れが困難である。適応型デザインは,臨床試験の確固たる計画の負担を軽減する手段としてとらえるべきではない。むしろ適応型デザインは,困難な実験条件に直面することが必須となるような領域で,臨床試験を計画する際の道具立てとして利用するのがもっとも適切な利用の場であろう。あらゆる場合において,(症例数の変更,処理群の中止など)予想されるタイプのデザイン修正を試験プロトコールに明記し,その妥当性を示さなければならない。適切な計画を行わずに適応が検証試験に導入されると,その試験自体が探索的なものとみなされてしまうことになる。適応型デザインを用いることは,事前に規定した第一種の過誤が統計手法により制御され,処理効果の正しい推定値と信頼区間が利用でき,異なったステージから得られる結果の一様性を評価する方法が,事前に計画されることが暗黙のうちに仮定されている。異なったステージからの結果を正当に結合できることを保証するためには,徹底した検討が必要である。最終的な推奨治療の決定を正当化する根拠の中身が議論されなければならない。試験デザインの変更の必要性ならびにデザイン変更そのものが結果の臨床解釈に影響を与える可能性について計画段階で検討しておく必要がある。
-
-
ORIGINAL ARTICLES
-
-
田七人参成分のサイトカイン(IL−1β)分泌抑制作用
36巻3号(2008);View Description Hide DescriptionThe aim of this research was to find the mechanism of anti−inflammatory effect and the properties of the active constituents of methanol extract of Panax notoginseng(Denchi)in vitro.Denchi(100μg/mL)inhibited the release of IL−1β(88%), INF−α(51%), IL−4(34%),INF−γ(28%), IL−10(27%), IL−6(13%)from PMBC. However, it did not change the IL−2 release, and increased the IL−5 release(48%). The fraction−C, in which denchi−specific ginsenosides were contained, showed strong and dose−related inhibition of IL−1β release (IC50=2.86μg/mL). However, the inhibitory activity of Panax ginseng−related ginsenosides (fraction−B)was extremely weak, 20% at 200μg/mL, as compared with that of the fraction−C.These results suggest that the anti−inflammatory effect of Denchi is achieved through an inhibition of the IL−1β release, and that the active compounds are highly lipid−soluble ginsenosides.(Jpn Pharmacol Ther 2008;36:191−8)KEY WORDS Panax notoginseng(Denchi), Ginsenosides, Cytokine, Inhibition of IL−1βrelease, PBMC cell, Anti−inflammatory effect -
CBEX−Dr 配合飲料の健常者における抗疲労効果
36巻3号(2008);View Description Hide DescriptionObjectives CBEX−Dr is a chicken breast extract containing imidazole dipeptides developed by Nippon Meat Packers, Inc. We investigated the effect of CBEX−Dr−containing drink on physical fatigue in healthy volunteers. Methods In a present double−blind, placebo−controlled, crossover trial, 20 healthy volunteers were randomized to oral CBEX−Dr or placebo administration for 29 days. No statistical differences in age, gender or body mass index(BMI)were shown between the two groups. Subjects took CBEX−Dr(imidazole dipeptides 400 mg)or placebo once a day for 29 days. As a fatigue−inducing physical task, subjects performed workload trials on a cycle ergometer at fixed workloads for 4 hours and then rested for 4 hours. We evaluated physical performance by 10−second high power test and subjective sensation of fatigue by visual analogue scale. Results Oral CBEX−Dr administration inhibited the decrease in physical performance and attenuated fatigue sensation by physical load. Conclusions CBEX−Dr is effective for the attenuation of fatigue and CBEX−Dr−containing drink is one of the promising candidates for anti−fatigue food. (Jpn Pharmacol Ther 2008;36:199−212) KEY WORDS CBEX−Dr, Imidazole dipeptide, Fatigue, Physical performance, Visual analogue scale -
健常者を対象とした CBEX−Dr 配合飲料の長期摂取における安全性
36巻3号(2008);View Description Hide DescriptionObjectives CBEX−Dr is a chicken breast extract containing imidazole dipeptides by Nippon Meat Packers, Inc. We investigated the safety of long−term administration of CBEX−Dr−containing drink in a parallel, randomized, double−blind and placebo−controlled study. Methods Forty−eight healthy subjects(24 females, 24 males, age 39.6±8.2 years old)were randomized in two groups so that there were no statistical differences in age, gender, body mass index(BMI)or visual analogue scale(VAS)score. The subjects took CBEX−Dr(imidazole dipeptides 400 mg)−containing drink or placebo once a day for 12 weeks. Results No adverse events which attributed to CBEX−Dr−containing drink were observed in results of blood examination, urinalysis, physical examination or careful evaluation by doctor. Moreover, CBEX−Dr−containing drink attenuated fatigue sensation. Conclusions Our present observations demonstrated the safety of long−term administration of CBEX−Dr−containing drink in healthy subjects.(Jpn Pharmacol Ther 2008;36:213−24)KEY WORDS CBEX−Dr, Imidazole dipeptide, Fatigue, Safety, Visual analogue scale -
健常者を対象とした CBEX−Dr 配合飲料の過剰摂取における安全性
36巻3号(2008);View Description Hide DescriptionObjectives CBEX−Dr is a chicken breast extract containing imidazole dipeptides by Nippon Meat Packers, Inc. We investigated the safety of excess administration of CBEX−Dr−containing drink in a parallel, randomized, double−blind and placebo−controlled study. Methods Forty−eight healthy subjects(24 females, 24 males, age 39.6±8.2 years old)were randomized in two groups so that there were no statistical differences in age, gender or body mass index(BMI). The subjects took CBEX−Dr(imidazole dipeptides 1200 mg)−containing drink or placebo once a day for 4 weeks. Results No adverse events which attributed to CBEX−Dr−containing drink were observed in results of blood examination, urinalysis, physical examination or careful evaluation by doctor. Conclusions Our present observations demonstrated the safety of excess administration of CBEX−Dr−containing drink in healthy subjects.(Jpn Pharmacol Ther 2008;36:225−35) KEY WORDS CBEX−Dr, Imidazole dipeptide, Excess administration, Safety -
高濃度茶カテキンの継続摂取が内臓脂肪型肥満女性の内臓脂肪およびメタボリックシンドロームリスクに及ぼす影響
36巻3号(2008);View Description Hide DescriptionBackground Visceral fat accumulation is thought to be an upstream factor of several metabolic disorders. Long−term ingestion of high dose green tea catechins was reported to reduce visceral fat. Objective We investigated the effect of long−term ingestion of beverage containing high dose green tea catechins for 12 weeks on the visceral fat and relating metabolic disorders in overweight/obese Japanese female whose visceral fat area was greater than 85 cm2. Methods Double−blind placebo controlled parallel trial was conducted. Subjects were recruited on the basis of visceral fat area measured by computer tomography and ingested 540 mg/500 mL catechin−containing beverage or placebo for 12 weeks. Results Significant decrease was observed in body weight, body mass index and waist circumference. Visceral fat area also decreased significantly in catechin group. Among the risk factors, systolic blood pressure and glycated hemoglobin(HbA1c)was decreased significantly only in catechin group. Conclusion Long−term ingestion of high dose catechin improved not only visceral fat accumulation but also some metabolic disorder and may be beneficial for the management of body fat and metabolic syndrome.(Jpn Pharmacol Ther 2008;36:237−45)KEY WORDS Green tea catechins, Visceral fat, Metabolic risk -
温州みかん由来β−クリプトキサンチン含有飲料摂取による体脂肪低減効果の有用性の検討
36巻3号(2008);View Description Hide DescriptionWe carried out the comparative trial by double blindness study to confirm the effect to the visceral fat of men(average:45.6±9.74 years old, average waist:93.31±7.014 cm)by feeding β−cryptoxanthin. By assimilating the drink including the β−cryptoxanthin 0.25 mg/100 mL that extracted from Satsuma mandarin decreased visceral fat more significantly in comparison with the placebo group.(Ingestion start 12 weeks for:13.158±9.314 cm2:p<0.01). During the study there was not any subjective symptom to all the subjects and also there was not even a side effects. From the aforementioned result, we concluded that β−cryptoxanthin improved the visceral fat of men, without any subjective symptom and also blood, urine inspection.(Jpn Pharmacol Ther 2008;36:247−53)KEY WORDS β−cryptoxanthin, Metabolic syndrome, Fat metabolism
-