Smith A L, Daum R S, Siber G R, Scheifele D W, Syriopoulou V P
Division of Infectious Disease, Children's Hospital and Medical Center, Seattle, Washington 98105.
Antimicrob Agents Chemother. 1988 Jul;32(7):1034-9. doi: 10.1128/AAC.32.7.1034.
We studied the effect of meningitis and the method of parenteral gentamicin administration (intramuscular injection, a 30-min intravenous infusion, or intravenous bolus administration) on achievable concentrations of drug in cerebrospinal fluid (CSF). In normal animals, only intravenous bolus administration of 2 to 8 mg/kg produced a gentamicin concentration of greater than 0.1 microgram/ml in CSF in some animals. All CSF samples contained less than the limit of detection (0.1 microgram/ml) after the intramuscular administration of 6 mg/kg. In animals with meningitis, gentamicin penetration into cisternal CSF was increased significantly after a bolus administration of 6 mg/kg (mean, 0.197 +/- 0.063 microgram/ml in normal animals versus 1.68 +/- 0.38 micrograms/ml in animals with meningitis; P less than 0.01). In meningitic animals that received 6 mg/kg as an intravenous bolus, lumbar CSF had the highest maximum concentration (4.25 +/- 1.08 micrograms/ml), in comparison with ventricular CSF (3.10 +/- 0.66 micrograms/ml). The gentamicin concentration in cisternal CSF decreased more slowly than it did in serum (elimination half-life, 238.70 +/- 64.56 min in cisternal CSF versus 82.73 +/- 2.91 min in serum), yielding a relative increase in the percentage of penetration. We conclude that maximum penetration by gentamicin into CSF occurs after intravenous bolus administration and that the maximum concentration occurs in lumbar CSF.
我们研究了脑膜炎以及庆大霉素胃肠外给药方法（肌内注射、30分钟静脉输注或静脉推注）对脑脊液（CSF）中可达到的药物浓度的影响。在正常动物中，只有静脉推注2至8mg/kg才能使部分动物脑脊液中的庆大霉素浓度大于0.1μg/ml。肌内注射6mg/kg后，所有脑脊液样本中的药物浓度均低于检测限（0.1μg/ml）。在患有脑膜炎的动物中，静脉推注6mg/kg后，庆大霉素向脑池脑脊液的渗透显著增加（正常动物平均为0.197±0.063μg/ml，患有脑膜炎的动物为1.68±0.38μg/ml；P<0.01）。在接受6mg/kg静脉推注的患脑膜炎动物中，腰段脑脊液的最高浓度（4.25±1.08μg/ml）高于脑室脑脊液（3.10±0.66μg/ml）。脑池脑脊液中庆大霉素浓度的下降速度比血清中慢（消除半衰期，脑池脑脊液为238.70±64.56分钟，血清为82.73±2.91分钟），导致渗透百分比相对增加。我们得出结论，庆大霉素静脉推注后脑脊液中的渗透最大，且最高浓度出现在腰段脑脊液中。
