Potentiation by the injection vehicle of the teratological action of acetazolamide in rats

Abstract

The high alkalinity of the injection vehicle of certain parenteral solutions of acetazolamide produces necrosis of the skin upon sc injection. The possible modification of this effect on the teratogenicity of acetazolamide was examined. Acetazolamide in a vehicle of pH 10.5 produced 36.6% fetal malforma tions, in a vehicle of pH 8.7, 6.1%, and in neutral suspension, 11.8%. Adrenal medullectomy or phentolamine plus the high pH acetazolamide reduced the fre quency to 23.2 and 24.4%, respectively. The teratogenicity of the low pH acet azolamide was increased by epinephrine to 64.2%. The frequency of hemimelia and micromelia, and of bilateral involvement, was greater in litters exposed to the high pH acetazolamide or the epinephrine‐acetazolamide combination, and was reduced by phentolamine or adrenal medullectomy. Neither the high pH vehicle nor epinephrine produced fetal defects in the absence of acetazolamide. The biological disposition of acetazolamide was not altered by any of the treat ments. Reduction of uterine blood flow may be responsible for the potentiation of teratogenicity by the high pH vehicle.