著者

馬場 茂雄

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.4, no.3-4, pp.279-287, 1973-12-30 (Released:2010-06-28)

参考文献数

21

著者

Osamu TANAKA Satoshi CHIDA Tetsuo KIMURA Teruo SAITO Ryuichi KATO

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics (ISSN:03881601)

巻号頁・発行日

vol.13, no.3, pp.463-475, 1982-09-30 (Released:2010-06-28)

参考文献数

24

被引用文献数

4 2

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A transdermal sustained release formulation. of isosorbide dinitrate (Frandol Tape) has been developed for the purpose of prolonging the preventive effect of isosorbide dinitrate (ISDN) against attacks of angina pectoris.The plasma levels of ISDN and the two metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate, were measured after the application of Frandol Tape (ISDN 40mg) in ten healthy male volunteers. After a single application of the tape to the breast for 24 or 48 hrs, the mean plasma levels of ISDN increased slowly to reach their peaks of 2.6 or 2.7 ng/ml at 6 hrs and declined very slowly to 1.9 ng/ml at 24 hrs or to 1.4 ng/ml at 48 hrs after the application. After removal of the tape, the mean plasma levels of ISDN declined with a half-life of 2.3 hrs.The area under the plasma level versus time curve (AUC) for ISDN per the amount of ISDN absorbed percutaneously after a transdermal administration was larger than after an oral administration. Probably because ISDN was not susceptible to“first-pass effect” in the cutaneous route. On the other hand, it was suggested that urinary excretion behavior after a transdermal administration was similar to that after an oral administration.These results demonstrated that Frandol Tape might be an useful transdermal sustained release formulation of ISDN for the prevention of angina pectoris, since the plasma level of ISDN is maintained constantly during the period of application.

著者

内田 直樹 小林 秀行 戸嶋 洋和 三邉 武彦 小林 真一

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 = Japanese journal of clinical pharmacology (ISSN:03881601)

巻号頁・発行日

vol.43, no.2, pp.57-64, 2012-03-31

参考文献数

13

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MSG203 was developed by Meiji Seika Pharma Co., Ltd. as a generic drug of paroxetine hydrochloride hydrate (Paxil^® Tablets). Paroxetine is mainly metabolized by CYP2D6.Therefore, in addition to the evaluation of bioequivalence between MSG203 and Paxil^®, the effects of CYP2D6 polymorphism on the pharmacokinetic (PK) parameters of plasma paroxetine were also investigated.<BR>Ninety-six Japanese healthy subjects aged 20-35 years participated in the study. The study was performed in 3 different groups: MSG5 group compared 2 tablets of MSG203 5 mg versus 1 tablet of Paxil^® 10 mg; MSG10 group compared 1 tablet of MSG203 10 mg versus 1 tablet of Paxil^® 10 mg; and MSG20 group compared 1 tablet of MSG203 20 mg versus 1 tablet of Paxil^® 20 mg. Bioequivalence between MSG203 and Paxil^® was confirmed in all three groups. The safety profiles of both drugs were also similar. The PK parameters after a single oral dose of MSG203 20 mg in subjects with different CYP2D6 phenotypes were as follows. Mean C_max (ng/mL) of paroxetine was 0.78 in ultra-rapid metabolizers (UM; n=1), 5.82 in extensive metabolizers (EM; n=24), and, 18.60 in intermediate metabolizers (IM; n=4). Mean AUC _t (ng•h/mL) was 7.93 in UM, 88.52 in EM, and 495.61 in IM. Similar PK profiles in these phenotypes were confirmed after a single oral dose of Paxil^®.<BR>In this study, plasma concentrations of paroxetine were very low because of the high clearance profile in UM subjects. Generally, inadequate treatment would occur in patients with the UM phenotype of CYPs. However, information on the PK profiles in different CYP phenotypes is insufficient. Evaluation of the PK profiles of drugs in different CYP phenotypes provides valuable information for clinical use of drugs that are metabolized by polymorphic enzymes.

著者

羽賀 道信 清野 忠紀

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.8, no.3, pp.365-370, 1977

著者

水嶋 雅子 横田 祥 石川 岳彦 華岡 由香里 〓野 繁雄 劔物 修

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.20, no.4, pp.777-781, 1989

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Effects of pre-operative administration of ranitidine on pH and volume of gastric juicewere evaluated in 54 children (mean age: 5.4±1.0 yr) who underwent elective surgeryunder general anesthesia. Simultaneously, bromazepam suppository was evaluated as a premedicationagent for pediatric patients. Patients were randomly divided into four groups, and premedication agents were given 2 hr prior to induction of anesthesia. Patients ingroup A received diazepam syrup (0.5 mg/kg P. o.) ahd those in group B received bromazepamsuppository (3 mg). Patients in groups C and D received ranitidine (1 mg or2 mg/kg i. m.) together with bromazepam suppository (3 mg). Following induction ofanesthesia, a gastric tube (10 Fr. or 12 Fr.) was passed and stomach contents were collectedand analyzed for volume and pH, which was repeated every hr until the end ofthe operation. The gastric pH at the induction of anesthesia was observed to be 2.5 orless in 70% of the patients of groups A and B, 13% of group C, and O% of group D.The volume of gastric contents was less than 0.4 ml/kg in 87% of ranitidine-treatedpatiehts (groups C and D), in 29% of group A, ahd in 60% of group B. It was thenconcluded that pre-operative administration of ranitidine caused a significant reduction ofboth acidity and volume of gastric contents, which will contribute to preventing or reducingaspiration pneumonitis during general anesthesia. Plasma ranitidine concentrationsmeasured by high-performance liquid chromatography revealed 228±32 ng/ml in group Cand 487±59 ng/ml in group D at the induction.of anesthesia. Sedation at the inductionof anesthesia was evaluated utilizing our original pediatric premedication score, whichconsists of 3 check points: quietness (very good, 3 ; good, 2 ; fair, 1 ; bad, 0); crying (no, 2 ; a little, 1 ; yes, 0); and i. v. root (under local anesthesia, 1 ; following induction ofanesthesia, 0). The averaged scores were 4.5±0.4 in group A, 4.2±1.9 in group B, 4.1±0.6 in group C, and 4.8±0.5 in group D, respectively. There was no significantdifference in the score in 4 groups. A plasma bromazepam level was 414±49 ng/ml at theinduction of anesthesia. Our results showed that bromazepam suppository is as effectiveas diazepam syrup for premedication in children.

著者

池田 泰子 平松 慎石 遠山 博 下里 公昭 荻原 篤 新津谷 真人 小林 明芳 長谷川 延広 村松 準 木川田 隆一

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.24, no.1, pp.147-148, 1993

著者

越前 宏俊

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.43, no.4, pp.235-239, 2012

著者

Brill Henry Jaffe Jerome H.

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.9, no.4, pp.445-460, 1978

被引用文献数

1

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米国での医薬品の乱用 (探索的および娯楽的使用) は1960年代に急激な増加を示し, 1970年代の初期にはすでにかなりの高レベルに達した.それ以来そのレベルは高いままにとどまっている.このことは調査結果から明らかであるが, 1972年以前にはこのような薬物の有害な影響を系統的に調査する体制は確立されていなかったのでそれ以前に関して確かなことはいえない.<BR>若年成人男子を中心とする数百数千の人達は, 過去に種々の医薬品を乱用した経験があり, あるいは現在乱用中である.最も広く用いられている医薬品はbarbiturates, amphetamine類およびbenzodiazepine系の抗不安薬である.この他にも合成鎮痛薬や全身麻酔薬などいろいろな医薬品が使われている.これらの薬物はalcoholやタバコと交互にあるいは同時に使われ, また医薬品以外のcocaineやheroin, 大麻, LSDおよびphencyclidineなどとも一緒に使われている.薬物摂取の初期体験は12ないし13歳という早い時期に始まり, 年齢を経るにしたがって使用頻度は増加する.その過程において最初害の少ない薬物から次第に害の大きな薬物に移行していく傾向がある.たとえば大麻の使用からamphetamine類やbarbituratesあるいは幻覚発現薬などの使用に移行している.Cocaineとheroinの乱用は最も常軌を逸したものとされている.またこれらの薬物を乱用している人たちは大抵amphetamine類, barbituratesあるいはもう少し程度のよい薬物などを一緒に用いている.<BR>米国社会では医薬品の乱用問題はalcoholや大麻問題の背後に隠れ, あまり注目されていないが, 要処法薬の乱用が薬物乱用問題に関する一般大衆の受けとめ方を悪化させていることは事実である.このように薬物乱用は広まっているにもかかわらず, 治療を必要とするような問題を起こす者は若年者の中ごく限られた少数であるという事実は注目に値する.いずれにしても最近はこのような治療を必要とする人々のための治療施設が全国的に設置されるに至った.治療を必要とする人達はしばしば薬物を大量かつ種々用い, また薬物乱用, alcohol乱用, 精神疾患, および社会的問題などが種々雑多にからみ合った複雑な状態にあるので施設はこれらの問題に対処しなければならない.<BR>薬物乱用問題が全国的な広がりを示した結果, 一般大衆のほとんどが大麻などを試みに使用することについてある程度許容するようになってきた.しかしこれらの人々も大麻を常用することを認めているわけではなく, またheroinその他の静脈内摂取薬物の乱用には強く反対している.<BR>成人の間の医薬品による依存に関しては, 伝統的な医療体系のもとに治療が行われている.政府は医薬品乱用の対策の一つとして短時間持続性のbarbituratesを医薬品市場から完全に一掃し, またamphetamineの医療適用を厳重に制限することを検討中である.これらの薬物が医師を通じて入手されているかどうか明らかではないが, 医薬品乱用全体のうちで短時間持続性のbarbituratesやamphetamine類の乱用が際立って多いことは認めざるを得ない.<BR>本席では, 公衆衛生上の配慮の妥当性という観点からこのような厳しい規制が立案されるもととなっている各種の問題点や根拠を紹介し, ますます厳しくなる政府の規制に対する反対意見の論旨を概括し, さらにまた, 米国における薬物乱用問題の対処の仕方がいかに米国社会特有の伝統的および政治的な体質に根ざしているかを明らかにしたい.

著者

橋本 健太郎 林 敬次 柳 元和 梅田 忠斎 浜 六郎

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.30, no.1, pp.199-200, 1999-01-31

著者

牛之濱 風見 柴山 良彦 本屋 敏郎 山田 勝士

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.34, no.1, pp.105S-106S, 2003-01-31

著者

深沢 英雄 本田 雅子 市下 浩子 清水 宏俊

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.9, no.3, pp.251-265, 1978

被引用文献数

3

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Blood level profiles of flunitrazepam and its N-desmethyl-metabolite were in vestigated after single and multiple administrations of flunitrazepam to groups of 5 healthy male adult volunteers. Urinary excretion of some major metabolites of flunitrazepam was also examined following oral doses of a single 4 mg.<BR>Following the oral administration, the absorption of flunitrazepam was fairly rapid: the peak times were attained within 1-2 hr with peak levels of 9.6-16.0 ng/ml for 2 mg dose and 20.6-30.3 ng/ml for 4 mg dose. The drug then disappear ed from the blood biphasically. The rate of disappearance was independent of the doses, while the AUC for the unaltered drug was dose-related. Blood levels of N-desmethyl flunitrazepam were always lower than those of the unal tered drug. 7-Amino-flunitrazepam and 3-hydroxy-flunitrazepam were major urinary metabolites, comprising about 9% and 5% of the dose, respectively, in the initial 72-hr urine. During repeated administration of the drug at a daily oral dose of 2 mg, the blood level profiles showed gradual elevation during the first few days, and then the steady-state was attained within 3-5 days.<BR>After i. v. injection of 2 mg, flunitrazepam was eliminated from the blood triphasically. The mean AUC for the unaltered drug obtained after the i. v. injection was about twice as much as that obtained after the oral administration of the identical dose.

著者

河合 昭悦 桑野 友彰 中島 久夫 水野 清史 西本 博之 久保田 信子

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 = JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS (ISSN:03881601)

巻号頁・発行日

vol.34, no.4, pp.193-198, 2003-07-31

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The major factors that have heretofore prevented an efficient implementation of clinical trials include deviations from the protocol at the investigator's site, defectiveness in filling out the case report forms (CRFs), frequent monitoring and fixing work of patient data by the sponsor, handwritten preparation of various documents, and so on.<BR>As an experiment in electronic implementation of an efficient clinical trial utilizing information technology, we formed an electronic data capture (EDC) system that efficiently collects clinical data from the investigator's site, and applied it to a clinical trial. As a result, there was no patient with a GCP violation and thus all were eligible as study subjects and the number of correction log form (CLF) for CRFs was considerably reduced. In addition, it was possible to conduct an efficient clinical trial and shorten the study period by utilizing this EDC system. We discuss the future readiness for clinical trials based on this experience of implementation, as well as the challenges that lie ahead.

著者

大須賀 恵美子 阿曽 亮子 大橋 和史 奈良 弘恵

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.30, no.1, pp.67-68, 1999-01-31

著者

大須賀 恵美子 阿曽 亮子 大橋 和史 奈良 弘恵 太田 詩穂子

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.32, no.2, pp.371S-372S, 2001-03-31