-transparent.png){kind=logo}
The steady state trough concentrations (Cmin) and pharmacokinetics of valproic acid were investigated in schizophrenic patients during the treatment of valproic acid, 200 mg, twice daily and after the one dose of 400 mg, respectively, with and without haloperidol (6 to 10 mg/day, N = 6) or chlorpromazine (100 to 300 mg/day, N = 6). Four to 5 Cmin were monitored just before the morning valproic acid dose for 3 to 4 days preceding the kinetic study. The overall Cmin of valproic acid with chlorpromazine (33.2 +/- 1.7 micrograms/ml, N = 25) was significantly (p less than 0.01) greater than without (27.1 +/- 1.4 micrograms/ml, N = 25). The majority of the mean valproic acid concentrations observed after the 400-mg dose were significantly (p less than 0.05 to 0.01) greater during the chlorpromazine treatment as compared to those without the phenothiazine. The mean t1/2 was shortened from 15.4 +/- 1.4 to 13.5 +/- 1.2 hours (p less than 0.05) with a comparable increase in the clearance from 7.18 +/- 0.38 to 8.32 +/- 0.34 ml/hour/kg (p less than 0.01) after the discontinuation of chlorpromazine. All the patients revealed an increase in the valproic acid clearance after the chlorpromazine therapy was discontinued. When viewed overall, such a trend as found in the chlorpromazine group was not observed in the haloperidol group. The results suggest that chlorpromazine, but not haloperidol, inhibits the metabolism of valproic acid. However, the clinical significance of the interaction awaits future study.
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
July 1989,
Biological psychiatry,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
September 1964,
Current therapeutic research, clinical and experimental,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
October 1979,
Psychopharmacology,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
June 1968,
Current therapeutic research, clinical and experimental,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
January 1983,
Clinical pharmacy,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
April 1993,
Biological psychiatry,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
December 1987,
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
September 1992,
Pharmacopsychiatry,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
August 1978,
Naunyn-Schmiedeberg's archives of pharmacology,
T Ishizaki, and
K Chiba, and
M Saito, and
K Kobayashi, and
R Iizuka
January 1990,
Schizophrenia bulletin,
