PHARMACOKINETICS OF METRONIDAZOLE AS DETERMINED BY BIOASSAY
PHARMACOKINETICS OF METRONIDAZOLE AS DETERMINED BY BIOASSAY
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DOI：
10.1128/aac.6.6.691
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发表时间：
1974-01-01
影响因子：
4.9
通讯作者：
KIRBY, WMM
中科院分区：
文献类型：
--
作者：
RALPH, ED;CLARKE, JT;KIRBY, WMM
本文描述了甲硝唑的药代动力学，甲硝唑是一种体外对大多数厌氧菌有效的药物，在治疗厌氧菌感染方面很有前途。采用琼脂孔扩散法测定了10名成年男性志愿者单次和多次给药后的血清和尿液水平，并以梭状芽孢杆菌作为厌氧条件下的试验生物。单次给药500 mg和250 mg后，血清峰值水平分别为11.5 μg/ml和6.2 μg/ml。肾清除率仅为10.2 ml/min / 1.73 m2, 24 h内不到20%的给药剂量作为活性药物从尿液中回收，平均血清半衰期为8.7 h，超滤法测定无蛋白结合。使用多剂量甲硝唑（500毫克，每天4次，250毫克，每天3次），血液水平在最初几次剂量逐渐升高，然后趋于平稳，在3至7天内没有明显的积累。250mg，每日3次，第3天上午8点前（前一次给药后12小时）血清水平平均为3.9 μg/ml，晚上8点前平均为5.7 μg/ml。对于较高剂量的500 mg（每天4次）方案，相应的最低血清水平在上午8点为13.1 μg/ml，在晚上8点为21.3 μg/ml。峰值水平将高出约10 μg/ml，并且由于大多数厌氧菌（包括脆弱拟杆菌）的最低抑制浓度低于6 μg/ml，因此这些浓度应该具有非常有效的治疗效果，即使对于严重感染也是如此。
The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 μg/ml and 6.2 μg/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 m2, and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 μg/ml, and before the 8 p.m. dose, 5.7 μg/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 μg/ml at 8 a.m. and 21.3 μg/ml at 8 p.m. Peak levels would have been about 10 μg/ml higher, and since the minimum inhibitory concentrations of most anaerobes includingBacteroides fragilisare less than 6 μg/ml, these concentrations should be highly effective therapeutically, even for severe infections.