Human intravenous pharmacokinetics and absolute oral bioavailability of cefatrizine
Human intravenous pharmacokinetics and absolute oral bioavailability of cefatrizine
复制标题
头孢曲嗪的人体静脉药代动力学和绝对口服生物利用度
DOI：
10.1128/aac.24.6.915
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发表时间：
1983
影响因子：
4.9
通讯作者：
J. Ximenez
中科院分区：
文献类型：
--
作者：
M. Pfeffer;R. Gaver;J. Ximenez
在一项交叉研究中，对正常男性志愿者静脉注射和口服头孢曲嗪，剂量水平为250、500和1，000 mg。在此范围内，静脉药代动力学呈剂量线性; 30分钟输注结束时的平均血浆峰浓度分别为18、37和75 μ g/ml，全身清除率为218 ml/min/1.73 m2，肾清除率为176 ml/min/1.73 m2，体内平均保留时间为1.11 h。完整头孢三嗪的累积尿排泄量为剂量的80%，半衰期范围为1 - 1.4 h。稳态分布容积为0.22 L/kg。口服给药时，头孢三嗪250和500 mg的绝对生物利用度为75%，1,000 mg的绝对生物利用度为50%。在1.4、1.6和2.0 h时，平均血浆峰浓度和达峰时间分别为4.9、8.6和10.2 μ g/ml，平均滞留时间为2.4、2.6和3.1 h，平均吸收时间为1.3、1.6和1.9 h。口服肾脏清除率和半衰期值与静脉内值一致。250 mg、500 mg和1，000 mg时，完整头孢三嗪的累积尿排泄量（占剂量的百分比）分别为60、56和42。假设500 mg和1，000 mg剂量之间缺乏口服剂量线性是由于通过可饱和转运过程吸收头孢曲嗪的成分。高剂量下的相对吸收将足够慢，在达到最大生物利用度之前将经过吸收“窗口”。预期在剂量超过500 mg时观察到的生物利用度降低不会有任何治疗意义，因为临床研究正在确定推荐的500 mg单位剂量方案的疗效。
Cefatrizine was administered intravenously and orally at dose levels of 250, 500, and 1,000 mg to normal male volunteers in a crossover study. Intravenous pharmacokinetics were dose linear over this range; mean peak plasma concentrations at the end of 30-min infusions were, respectively, 18, 37, and 75 micrograms/ml, total body clearance was 218 ml/min per 1.73 m2, renal clearance was 176 ml/min per 1.73 m2, and mean retention time in the body was 1.11 h. Cumulative urinary excretion of intact cefatrizine was 80% of the dose, and half-lives ranged from 1 to 1.4 h. Steady-state volume of distribution was 0.22 liters/kg. On oral administration, the absolute bioavailabilities of cefatrizine were 75% at 250 and 500 mg and 50% at 1,000 mg. The mean peak plasma concentrations and peak times were, respectively, 4.9, 8.6, and 10.2 micrograms/ml at 1.4, 1.6, and 2.0 h, mean residence times were 2.4, 2.6, and 3.1 h, and mean absorption times were 1.3, 1.6, and 1.9 h. Oral renal clearance and half-life values corresponded well to the intravenous values. Cumulative urinary excretion of intact cefatrizine (as percentage of dose) was 60 at 250 mg, 56 at 500 mg, and 42 at 1,000 mg. It is hypothesized that the lack of oral dose linearity between the 500- and 1,000-mg doses is due to a component of cefatrizine absorption by a saturable transport process. Relative absorption at the high dose would be sufficiently slow that an absorption "window" would be passed before maximum bioavailability could be attained. It is not expected that the observed bioavailability decrease at doses exceeding 500 mg will have any therapeutic significance, since clinical studies are establishing efficacy for a recommended unit dosage regimen of 500 mg.