Safety of nelfinavir use during pregnancy. An experimental approach in rats.

This experimental study aimed to evaluate the safety of nelfinavir when administered in normal up to high doses during the entire period of rat pregnancy. The renal and liver compartments of both mothers and fetuses were studied. For this purpose, three groups of pregnant rats were treated with nelfinavir (E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg; no. = 10 in every group) from "zero" up to the 20th day of gestation. These doses were divided into two daily administrations by gavage. Controls (no. = 10) received distilled water in the same schedule. At term-pregnancy, the rats were deeply anesthesized and blood samples were collected for alanine and aspartate aminotransferases, creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and processed for histopathological study. In all groups blood transaminases were within the normal limits, as were the levels of creatinine and urea, thus indicating that the treatment with nelfinavir during the entire gestation was essentially devoid of liver or kidney effects which could result in altered metabolic parameters. Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilatation. It is concluded that only doses of nelfinavir used during the entire gestation in doses well above the usual human doses could be considered to be potentially hepatotoxic for the pregnant rat.