Nix D E, Wilton J H, Velasquez N, Budny J L, Lassman H B, Mitchell P, Divan K, Schentag J J
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York 14209.
J Antimicrob Chemother. 1992 Apr;29 Suppl A:51-7. doi: 10.1093/jac/29.suppl_a.51.
Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture. Serum and CSF cefpirome concentrations were determined by high performance liquid chromatography. The mean maximal serum concentration of cefpirome was 264 +/- 76 mg/L. A mean steady-state volume of distribution of 20 +/- 4 L, clearance of 7.4 +/- 1.3 L/h, and half-life of 2.5 +/- 0.5 h were determined. Mean CSF concentrations were 0.50 +/- 0.11 mg/L at 1-2 h post dose (n = 4), 0.57 +/- 0.13 mg/L at 2-4 h post dose (n = 4), 0.76 +/- 0.34 mg/L at 4-6 h post dose (n = 7), and 0.83 +/- 0.29 mg/L at 6-8.3 h post dose (n = 5). Blood:brain barrier permeability to cefpirome may not be a limiting factor as CSF concentrations were rapidly attained. Further studies are required to determine the mechanism of cefpirome transport between plasma and CSF.
选取20例计划行选择性脊髓造影或脊髓麻醉的患者（平均年龄52±12岁，平均体重75±15kg），以确定新型广谱头孢菌素抗生素头孢匹罗（HR - 810）的脑脊液穿透性。在腰椎穿刺前1至8小时，静脉推注单剂量2g头孢匹罗。在15个预定时间采集血样，并在腰椎穿刺时采集一份脑脊液样本。通过高效液相色谱法测定血清和脑脊液中头孢匹罗的浓度。头孢匹罗的平均最大血清浓度为264±76mg/L。确定平均稳态分布容积为20±4L，清除率为7.4±1.3L/h，半衰期为2.5±0.5h。给药后1 - 2小时脑脊液平均浓度为0.50±0.11mg/L（n = 4），2 - 4小时为0.57±0.13mg/L（n = 4），4 - 6小时为0.76±0.34mg/L（n = 7），6 - 8.3小时为0.83±0.29mg/L（n = 5）。由于脑脊液浓度能迅速达到，血脑屏障对头孢匹罗的通透性可能不是限制因素。需要进一步研究以确定头孢匹罗在血浆和脑脊液之间转运的机制。
