Immunotoxicity evaluation of nelfinavir in rats.

The objective of these investigations was to determine whether exposure to the HIV-1 protease inhibitor nelfinavir compromises immune function in Sprague Dawley rats. Animals (20/sex per group) were exposed orally for 1 or 6 months to nelfinavir at doses of 0 (1% carboxymethylcellulose vehicle), 100, 300 or 1000 mg/kg per day. Animals were observed daily for morbidity/mortality and for clinical signs of toxicity. Body weights were recorded weekly (weeks 1-14) and then monthly there-after and at study termination. At termination (1 month or 6 months; 10/sex per group), serum was collected and retained for toxicokinetic analysis. The spleen, thymus and liver were removed from each animal and weighed; thymuses and liver were discarded after weighing. Spleens were prepared and immunophenotyping, natural killer (NK) cell activity, and proliferative responses to mitogenic stimuli (e.g., concanavalin A, Salmonella typhimurium) were evaluated. There were no treatment-related effects on immune cell populations (ab...