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This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12. Dams were then exposed continuously to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments during gestation days 5-12, in order to determine if hyperoxic maternal conditions offered a protective environment for the fetus, and conversely, if hypoxia exacerbated teratogenicity. Dams were sacrificed on gestation day 18, and litter and fetal data were collected. It was determined in separate groups under normoxic conditions that the osmotic minipump system maintained VA plasma levels corresponding to human therapeutic levels. Sodium valproate was found to induce developmental toxicity in the CD-1 mouse fetus at human therapeutic drug plasma levels. Fetal weights were reduced, and the number of resorptions, deaths, and hematomas was increased. While hypoxia exacerbated the toxic effect on the fetus, hyperoxia failed to ameliorate the outcome.
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
October 1990,
Acta paediatrica Japonica : Overseas edition,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
January 1992,
Journal of craniofacial genetics and developmental biology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
January 1991,
Journal of craniofacial genetics and developmental biology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
June 1987,
Neuropharmacology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
November 1989,
Teratology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
January 1988,
Teratogenesis, carcinogenesis, and mutagenesis,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
January 1984,
Psychopharmacology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
October 1992,
International journal of immunopharmacology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
December 1997,
European journal of morphology,
R B Paulson, and
M E Sucheston, and
T G Hayes, and
H S Weiss, and
L A Sachs, and
M Oca, and
B Kernan, and
S Weiss
October 1999,
Cellular and molecular life sciences : CMLS,
