title: Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears.
abstract: OBJECTIVE
  To quantitatively describe the pharmacokinetics of valproic acid (VPA) in guinea pig serum (total [Cf+b] and free [Cf]), cerebrospinal fluid (CSF) [C]CSF and tears [C]T using a simple kinetic model, and to examine whether [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters.
  
  
  METHODS
  [Cf+b], [Cf], [C]CSF and [C]T were determined after bolus i.v. injection of 10 or 20 mg/kg VPA using GC/ECNCI/MS.
  
  
  RESULTS
  [Cf+b] could be quantitatively described by a two compartment model with linear elimination kinetics. [Cf] was separately analyzed using multi-exponential equations. [C]CSF was analyzed using a simple kinetic model in which the CSF compartment is independently connected with the serum compartment by the apparent diffusion constants (KINCSF and KOUTCSF). [C]T was analyzed using the same simple kinetic model used for [C]CSF. The values of [C]CSF and [Cf] in the steady state can be represented by the following equations; [C]CSF = KINCSF/KOUTCSF x [Cf], [Cf] = KOUT/KINT x [C]T, and indicating that [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters.
  
  
  CONCLUSIONS
  The measurement of [C]T which can be collected non-invasively and estimated the pharmacokinetic parameters for [Cf], [C]CSF, and [C]T might be a very useful method for TDM of VPA.
authors.affiliation: Department of Pharmaceutics, Niigata College of Pharmacy, Japan. sato@niigata-pharm.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Kitagawa
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: A
authors.initials: A
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D006168:Guinea Pigs; D008297:Male; D013666:Tears / Q000378:metabolism*; D014635:Valproic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid