Lipid peroxidation-independent mechanisms of vitamin e-mediated protection against cyclosporine a-induced hepatocellular toxicity and apoptosis.

Cyclosporine A (CsA) produces oxidative stress and apoptosis in rat hepatocytes, but it is not known whether membrane lipid peroxidation plays a role in CsA toxicity. The objective of the present study was to determine whether iron-catalyzed hydroxyl or membrane alkoxyl radical formation is causally involved in the prooxidative cell injury and apoptosis. As previously reported, cultured rat hepatocytes exposed to CsA exhibited concentration-dependent signs of apoptotic cell injury, including chromatin condensation and fragmentation, increased caspase-3 activity, and release of cytosolic lactate dehydrogenase.

Role of antioxidants in the O-hydroxyethyl-D-(Ser)8-cyclosporine A (SDZ IMM125)-induced apoptosis in rat hepatocytes.

The mechanisms underlying the apoptotic activity of the immunosuppressive drug cyclosporine A and its O-hydroxyethyl-D-(Ser)(8)-derivative SDZ IMM125 in rat hepatocytes are not yet fully understood. It was the purpose of the present study to investigate the role of anti- and pro-oxidants and of caspase-3 and intracellular Ca(2+) in SDZ IMM125-induced apoptosis in rat hepatocytes. SDZ IMM125 induced an increase in chromatin condensation and fragmentation, and the activation of caspase-3.

Pharmacokinetics and pharmacodynamics of saquinavir in pediatric patients with human immunodeficiency virus infection.

Objective: Our objective was to investigate the clinical pharmacologic characteristics of saquinavir given as a soft gelatin capsule, either alone or in combination with nelfinavir, to children and adolescents with human immunodeficiency virus infection.

Methods: The pharmacokinetics of 50 mg/kg saquinavir 3 times a day (tid) alone versus 33 mg/kg saquinavir tid plus 30 mg/kg nelfinavir tid was assessed after single-dose administration and after short- and long-term administration. The single-dose pharmacokinetics of fixed (1200 mg) versus unrestricted weight-adjusted dosing (50 mg/kg) was also investigated.