Gentamicin penetration into cerebrospinal fluid in experimental Haemophilus influenzae meningitis.
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.
Smith
A L
AL
Division of Infectious Disease, Children's Hospital and Medical Center, Seattle, Washington 98105.
Daum
R S
RS
Siber
G R
GR
Scheifele
D W
DW
Syriopoulou
V P
VP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid*
D005839:Gentamicins