A single administration of recombinant human interleukin-12 is associated with increased expression levels of interferon-gamma and signal transducer and activator of transcription in healthy subjects.

The objectives of this study were to assess the safety and tolerability of single doses of 1, 4, and 8 mug of recombinant human interleukin-12 (rhIL-12) administered subcutaneously to healthy subjects. The pharmacokinetics, pharmacodynamics, and pharmacogenomics of rhIL-12 were evaluated. Recombinant human IL-12 was well tolerated in these healthy male and female subjects. The most frequently reported adverse events were flu-like symptoms, which exhibited a dose-response relationship. Pharmacokinetic analysis suggested that serum IL-12 levels increased with dose. Analysis of serum levels indicated that interferon-gamma increased with the dose of rhIL-12, whereas IL-6 levels showed no changes with rhIL-12 treatment. The messenger ribonucleic acid expression of signal transducer and activator of transcription was significantly increased 24 hours after the administration of rhIL-12 for all dose groups versus placebo, and results indicated that the magnitude of increase may be dose dependent. This study suggests that interferon-gamma and signal transducer and activator of transcription are biomarkers of rhIL-12 activity.

Multiple-dose, safety, pharmacokinetics, and pharmacodynamics of a new selective estrogen receptor modulator, ERA-923, in healthy postmenopausal women.

ERA-923 is a new selective estrogen receptor modulator under clinical investigation for use in tamoxifen refractory metastatic breast cancer. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal females. ERA-923 was well tolerated, and adverse events were mild and reversible. No clinically significant changes in laboratory values were found with ERA-923 versus placebo. ERA-923 appeared to undergo extensive metabolism and enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had no uterine or ovarian changes when evaluated with transvaginal ultrasound and compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in postmenopausal women dosed for 28 days.