J Korean Med Sci.  1990 Mar;5(1):39-45. 10.3346/jkms.1990.5.1.39.

Kinetics of Isoniazid Transfer into Cerebrospinal Fluid in Patients with Tuberculous Meningitis

• Shin SG
• Roh JK
• Lee NS
• Shin JG
• Jang IJ
• Park CW
• Myung HJ

• KMID: 1421477
• DOI: http://doi.org/10.3346/jkms.1990.5.1.39

Abstract

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.

Keyword

Isoniazid; Acetylisoniazid; Pharmacokinetics; Pharmacokinetic-Pharmacodynamic model; CSF level; CSF/Plasma partitioning

MeSH Terms

Administration, Oral
Humans
Isoniazid/*cerebrospinal fluid
Metabolic Clearance Rate
Models, Biological
Tuberculosis, Meningeal/*cerebrospinal fluid
Isoniazid