臨床薬理
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
29 巻, 6 号
選択された号の論文の4件中1~4を表示しています
  • 早川 弘一, 新 博次
    1998 年 29 巻 6 号 p. 837-841
    発行日: 1998/11/30
    公開日: 2010/06/28
    ジャーナル フリー
  • 新GCP下の治験におけるIRBの役割
    大須賀 恵美子, 阿曽 亮子, 大橋 和史, 奈良 弘恵
    1998 年 29 巻 6 号 p. 843-853
    発行日: 1998/11/30
    公開日: 2010/06/28
    ジャーナル フリー
    Under the new GCP, IRB should conduct continual reviews of each ongoing trial. Inthe Nippon Medical School Hospital, the IRB office is set up in the Clinical Pharmacology Center. We have examined the quality of clinical trials through simulated monitoringand auditing in Nippon Medical School Hospital from October to December, 1997. Nineclinical trials which included eleven patients were investigated. We checked the following13 items in the clinical trials: 1) progression of the trial, 2) investigators' documents, 3) existence of patients, 4) choice of investigators, 5) consent forms, 6) observanceof standards for registaration, 7) observance of standards for exclusion, 8) medicalexaminations, 9) utilized source documents, 10) accuracy of case report forms (CRFs) and source documents, 11) adverse events which should be reported, 12) correction in CRF, 13) observance of the IRB's requirements. All trials were properly executed withrespect to the existence of patients, consent forms, reported adverse events, correctionsin CRF, and observance of the IRB's requirements.
    Using the list of 13 items, we could check on three aspects of the clinical trialsincluding the drug, the protocol and the investigator's procedures, and evaluate thequality of the clinical trials. IRB monitoring is very important to ensure the quality ofclinical trials in a hospital. Moreover, IRBs must be independent of the investigators andthe sponsors, and should develop and follow appropriate procedures for the continuationof the review after approval and the start of the clinical trials.
  • Shigeyuki NAKANO, Hajime NAKASHIMA, Shunji MATSUKI, Naoto UEMURA, Seij ...
    1998 年 29 巻 6 号 p. 855-861
    発行日: 1998/11/30
    公開日: 2011/02/25
    ジャーナル フリー
    Objective: Aminoglycoside antibiotics such as gentamicin have unique characteristicssuch as a strong bactericidal effect especially against gram-negative bacilli, synergisticeffects when in used combination with β-lactam antibiotics, and a postantibiotic effect (PAE). Therefore they are still widely used for the treatment of serious infection. As thetherapeutic range of gentamicin is narrow, therapeutic drug monitoring (TDM) isrecommended to avoid adverse effects such as nephrotoxicity and ototoxicity.Gentamicin is eliminated through the kidney in an unchanged form. It is reported thatcreatinine clearance depends on the time-of-day in man. Although chronopharmacokineticfindings of the drug have been reported in rodents, it is not known at presentwhether this is also the case in man or not. The purpose of this study was to clarify theeffects of the time-of-day of drug administration on the pharmacokinetics of gentamicinin man.
    Methods: Nine healthy male volunteers were administered gentamicin, 80 mg/body, intramuscularly at three different times of day with a washout period of more than threedays (morning ; 8: 00, evening ; 16: 00, night ; 0: 00). The subjects were randomizedusing Latin square design to receive the drug at the three different times of day.Pharmacokinetic parameters were calculated using the one compartment model withfirst order absorption.
    Results: Although no difference was found in Cmax and tmax of the drug among thethree dosing times, clearance of the drug at midnight was significantly lower comparedwith the other two dosing times (morning: 4.71±0.25 L/hr, evening: 4.60±0.12 L/hr, night: 4.26±0.16L/hr, mean±S. E. p <0.05). In accordance with the lower clearanceat night, the half life of the drug at night was significantly longer (morning: 1.49±0.08hr, evening: 1.52±0.11 hr, night: 1.75±0.10 hr, mean±S. E. p<0.05).
    Conclusions: Clearance of gentamicin depends on the time-of-day of drug administration, showing a lower clearance at night in man. This temporal variation in thepharmacokinetics of gentamicin might be clinically important in patients with someclinical situations such as renal impairment.
  • 単回および反復投与試験における安全性と薬物動態の検討
    柴田 久雄, 新井 重紀, 井澤 美苗, 村崎 光邦, 高松 康雄, 井澤 修, 高橋 千寿子, 田中 正彦
    1998 年 29 巻 6 号 p. 863-876
    発行日: 1998/11/30
    公開日: 2010/06/28
    ジャーナル フリー
    The safety and pharmacokinetics of MCI-186 (edaravone, 3-methyl-1-phenyl-2-pyrazolin-5-one), a novel agent for cerebrovascular disease, were investigated in healthymale volunteers following a single intravenous infusion at doses of 0.2, 0.5, 1 .0, 1.5 and 2.0mg/kg and after 7 days of repeated administration at a dose of 1.0 mg/kg per day. Eachstep was studied in 7 volunteers (active drug: 5, placebo: 2).
    In clinical laboratory tests, the increases of serum total bilirubin at a dose of 0.2 mg/kg and placebo in one each, and a decrease of serum platelet count at a dose of 0.5 mg/kg were observed. No other apparent changes were observed in any subject. MCI-186 hada good tolerability profile in healthy volunteers.
    The plasma concentrations after a single intravenous infusion for 40 min (0.2-1 .5mg/kg) reached maximum levels (222.53-3060.73ng/ml) at 40min after the beginningof infusion, and then decreased rapidly with half-lives of 0.15-0.17 hr (t1/2α) and 1.45 hr (t1/2β) at doses of 0.2mg/kg and 0.5mg/kg, and 0.17 hr (t1/2&alpha;), 0.81-0.85 hr (t1/2β) and4.50-5.16 hr (t1/2γ) at doses of 1.0mg/kg and 1.5mg/kg. The Cmax and AUC increasedproportionally to doses from 0.2mg/kg to 1.5mg/kg.
    The plasma concentrations after a single intravenous infusion for 3 hr reached amaximum level (1225.96 ng/ml) at 3 hr after the beginning of infusion, and then decreasedrapidly with half-lives of 0.12 hr (t1/2α), 0.65 hr (t1/2β) and 4.38 hr (t1/2γ) at adose of 2.0 mg/kg. These plasma concentrations corresponded to those calculated fromthe pharmacokinetic parameters obtained by the analysis of plasma concentrations aftera single intravenous infusion for 40 min at a dose of 1.5 mg/kg.
    The plasma concentrations after repeated intravenous infusions for 40 min reachedmaximum levels (1616.21-1819.13 ng/ml) 40 min after the beginning of infusion, andthen decreased rapidly in a similar manner with a single intravenous infusion for 40 min.
    MCI-186 was metabolized and excreted rapidly in urine within 24hr after thebeginning of infusion. Urinary excretion rates of MCI-186, sulfate and glucuronide were0.56-0.98%, 5.61-13.16% and 68.64-83.17% of the dose, respectively. Irrespective of thedose and infusion time, urinary excretion rates of MCI-186 and its conjugates werealmost the same.
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