Footnotes

• Send reprint requests to: Dr. K. W. Riggs, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3. E-mail:riggskw{at}interchange.ubc.ca

• These studies were supported by funding from the Medical Research Council of Canada. H.W. was the recipient of a Pharmaceutical Manufacturers Association of Canada/-Health Research Foundation and Medical Research Council Graduate Scholarship in Pharmacy. S.K. was the recipient of a University of British Columbia Graduate Fellowship. D.W.R. is the recipient of an investigatorship award from the British Columbia Children's Hospital Foundation.

• Abbreviations used are::

  VPA

  valproic acid

  AIC

  Akaike's information criterion

  AUC_0–∞

  area under the curve of arterial plasma concentration-time profile

  AUC 0–∞u

  AUC_0–∞ of unbound drug

  C_b

  protein bound drug concentration

  CL_int

  intrinsic clearance

  CL_tb

  total body clearance of the total drug

  CL tbu

  total body clearance based upon unbound drug concentrations

  C_u

  unbound drug concentration

  Cmidu

  unbound plasma concentration at the midpoint of the urine collection interval

  CV

  coefficient of variation

  f_p

  area weighted unbound fraction of the drug

  f_u

  unbound fraction

  t_mid

  time at the midpoint of the urine collection interval

  Vd_ss

  steady-state volume of distribution

  Vd ssu

  steady-state volume of distribution based upon unbound drug concentrations

  Vd_ss′

  steady-state volume of distribution corrected for the effects of saturable protein binding

  2-ene VPA

  2-n-propyl-2-pentenoic acid

  3-ene VPA

  2-n-propyl-3-pentenoic acid

  4-ene VPA

  2-n-propyl-4-pentenoic acid

  3-keto VPA

  2-n-propyl-3-oxopentanoic acid

  4-keto VPA

  2-n-propyl-4-oxopentanoic acid

  3-

  4-, and 5-OH VPA, 3-, 4-, and 5-hydroxy VPA, respectively

  2-PSA

  2-propylsuccinic acid

  2-PGA

  2-propylglutaric acid

• • Received August 18, 2000.
  • Accepted January 11, 2001.