Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity.
Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.
Capece
B P S
BP
Departament de Farmacologia, de Terapèutica i de Toxicologia, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
Navarro
M
M
Arcalis
T
T
Castells
G
G
Toribio
L
L
Perez
F
F
Carretero
A
A
Ruberte
J
J
Arboix
M
M
Cristòfol
C
C
D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000662:veterinary*; D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001842:Bone and Bones / Q000002:abnormalities* / Q000196:embryology; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D017880:Limb Deformities, Congenital / Q000139:chemically induced / Q000662:veterinary; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000871:Anthelmintics; D015766:Albendazole; C027186:albendazole sulfoxide