Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis.
For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.
Shin
S G
SG
Department of Pharmacology, Seoul National University College of Medicine.
Roh
J K
JK
Lee
N S
NS
Shin
J G
JG
Jang
I J
IJ
Park
C W
CW
Myung
H J
HJ
D000284:Administration, Oral; D006801:Humans; D007538:Isoniazid / Q000134:cerebrospinal fluid*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid*
D007538:Isoniazid