Phase I Clinical Study of MCI-186(Edaravone, 3-methyl-1-phenyl-2-pyrazolin-5-one) in Healthy Volunteers: Safety and Pharmacokinetics of Single and Multiple Administrations.

Shibata, Hisao; Arai, Shigenori; Izawa, Minae; Murasaki, Mitsukuni; Takamatsu, Yasuo; Izawa, Osamu; Takahashi, C; Tanaka, Masahiko

doi:10.3999/jscpt.29.863

Cited by 35 publications

(32 citation statements)

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“…An isotopelabeling method was used to determine the concentration of edaravone in urine, but it could only be used to measure the urinary concentrations during the first 2 hours. [20] This is consistent with the results of our study. Edaravone is excreted as the unmetabolized drug (~1%) or is metabolized by sulfation (5-13%) or glucuronidation (68-83%) and excreted in urine within 24 hours of administration.…”

Section: Discussionsupporting

confidence: 83%

“…Edaravone is unstable in human plasma in air, [23] and the extraction method always takes more than 30 minutes, meaning that edaravone is exposed to air for a long time. [20] 3. In a preliminary experiment, we found that edaravone in human plasma was unstable when stored at room temperature for more than 45 minutes.…”

Section: Discussionmentioning

confidence: 99%

“…The C max values (table II) were significantly higher than the values reported in a previous study (C max 222.53 -16.77 ng/mL, dosage 0.2 mg/kg; C max 658.89 -96.88 ng/mL, dosage 0.5 mg/kg; C max 1727.19 -210.88 ng/mL, dosage 1.0 mg/kg; and C max 3060.73 -236.88 ng/mL, dosage 1.5 mg/kg). [20] The related explanations are as follows: 1. The intravenous infusion time in our study was 30 minutes, while in the previous study it was 40 minutes.…”

Section: Discussionmentioning

confidence: 99%

“…After receiving oral and written explanations of the study, the subjects gave written informed consent prior to starting the study. All subjects (15 males and 15 females) were recruited into three edaravone dose groups (20,30, and 60 mg). The volunteers who had been given a 30 mg single dose continued to receive multiple administrations from the second day, twice daily for 5 days.…”

Section: Design and Demographic Characteristicsmentioning

confidence: 99%

“…[19,20] These two methods are feasible but have their limitations. The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers.…”

Section: Introductionmentioning

confidence: 99%

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Phase I Clinical Study of Edaravone in Healthy Chinese Volunteers

Wang

et al. 2012

Drugs R D

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Objective: The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers. Methods: A total of 30 subjects (15 males and 15 females) were recruited and randomly assigned to three groups receiving edaravone doses of 20, 30, and 60 mg. All subjects received a single dose of edaravone during a 30-minute period, and only the 30 mg dose group continued to receive the same dose successively by intravenous infusion twice daily for the next 5 days. Plasma concentrations of edaravone were monitored by high-performance liquid chromatography at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600, and 720 minutes after edaravone administration. Results: The area under the plasma concentration-time curve during a dosage interval (AUC t ) values of the single dose in the 20, 30, and 60 mg dose groups were 3.64 -1.37, 5.17 -0.93, and 11.25 -3.42 mg Á h/L, respectively, while in the group receiving repeated dosing of 30 mg, the mean AUC t value was 5.06 -0.89 mg Á h/L. The corresponding maximum plasma drug concentration (C max ) values were 1599.0 -382.6, 2378.7 -316.7, and 4540.1 -901.1 ng/mL, respectively, in the single-dose groups, and 2479.1 -477.9 ng/mL in the 30 mg repeated-dose group. The mean AUC t and C max ratios between the repeated-dose group and the single-dose groups were 0.98 and 1.04. All laboratory test abnormalities (including increased alanine transaminase and triacylglycerol levels, and decreased white blood cell counts and creatinine levels) were mild and tolerable. All abnormal blood biochemical indices returned to normal levels after 7 days. Conclusion: Edaravone was safe and well tolerated in the volunteers and displayed linear increases in the C max and AUC t values.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Design and Demographic Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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