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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


  1. Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis. Shin, S.G., Roh, J.K., Lee, N.S., Shin, J.G., Jang, I.J., Park, C.W., Myung, H.J. J. Korean Med. Sci. (1990) [Pubmed]
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