-transparent.png){kind=logo}
A specific gas chromatographic assay has been developed for measurement of valproic acid (VPA) and its major conjugated metabolites. In rats given single intravenous doses, the decline in blood concentration of VPA was dose-dependent and followed first-order kinetics only at the lowest dose. The time required for the maximum concentration of VPA, after completion of the brief distribution phase, to decline by 50% was 11.7, 41 and 125 min at doses of 15, 150 and 600 mg of NaVPA per kg, respectively. A secondary increase in drug concentration, abolished by exteriorization of the bile, was observed in all intact rats with all doses. Some 45 to 55% of the dose appeared in the bile in 5 hr as VPA glucuronide. Urinary excretion of VPA glucuronide in intact animals accounted for 23 and 51% of the 15 and 150 mg/kg doses, respectively. Tissue distribution studies in rats sacrificed 20 and 90 min after dosage with [14C] NaVPA (150 mg/kg) showed that the drug concentration was highest in blood, moderate in liver, kidney, heart and lung and low in brain, fat, testis and skeletal muscle. During this interval the drug concentration declined in all tissues, whereas the total conjugated metabolites in the small intestine increased from 7 to 28% of the administered dose. The large intestine contained 30 times as much free drug as conjugate. Reabsorption of free VPA, released by hydrolysis of conjugate in the large bowel, accounted for the secondary rise in concentration of VPA observed in blood after single doses. The major urinary metabolites, VPA-glucuronide and 2-n-propylgutaric acid, were identified by gas chromatography/chemical ionization mass spectrometry. Sodium VPA caused a dose-dependent stimulation of bile flow, the magnitude and duration of which closely followed the blood concentration of VPA.
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
April 1991,
Journal of pharmacokinetics and biopharmaceutics,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
January 1981,
Hepatology (Baltimore, Md.),
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
December 1991,
Journal of pharmaceutical sciences,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
March 1983,
Research communications in chemical pathology and pharmacology,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
July 1989,
Clinical pharmacology and therapeutics,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
May 2016,
Drug metabolism reviews,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
July 2002,
The Journal of pharmacology and experimental therapeutics,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
January 1974,
Drug metabolism and disposition: the biological fate of chemicals,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
October 1990,
Journal of pharmacobio-dynamics,
R G Dickinson, and
R C Harland, and
A M Ilias, and
R M Rodgers, and
S N Kaufman, and
R K Lynn, and
N Gerber
December 1984,
Toxicology letters,
