An overview of animal toxicology studies with bicalutamide (ICI 176,334).

The toxicological profile of bicalutamide in animals following acute and chronic dosing is closely associated with the drug's non-steroidal anti-androgenic pharmacological activity. Bicalutamide produces typical effects of an anti-androgen, including atrophy of the prostate, testis and seminal vesicles and Leydig cell hyperplasia resulting from inhibition of pituitary feedback by testosterone. Subsequent benign Leydig cell tumors were seen in rats, but Leydig cell hyperplasia has not been observed in patients.

Long-term effects of an inotropic phosphodiesterase inhibitor (ICI 153,110) on the rat salivary gland, harderian gland, and intestinal mucosa.

The inotropic vasodilator, ICI 153,110, a phosphodiesterase inhibitor intended for the treatment of congestive heart failure, was administered to Alderley Park Wistar-derived rats for periods of up to 182 days. Treatment produced hypertrophy of salivary glands, hyperplasia of intestinal mucosa, and dacryoadenitis of the harderian gland. As the functions of these glandular tissues can be modified by factors which alter cyclic nucleotide metabolism, it is postulated that the glandular alterations produced by ICI 153,110 occurred as a result of phosphodiesterase inhibition.

Pathologic changes in blood vessels following administration of an inotropic vasodilator (ICI 153,110) to the rat.

ICI 153,110 is an inotropic vasodilator compound intended for the treatment of congestive heart failure. It was administered to rats at dose levels of 5, 10, and 250 mg/kg/day for up to 6 months as part of its preclinical development program. Detailed clinical investigations were conducted during the course of the study and histopathological examination took place after 28 days and 182 days of treatment as well as 42 days following cessation of dosing.