Based on our data, we cannot recommend using serum HER2 ECD levels to make trastuzumab or other treatment decisions for individual patients with advanced/metastatic breast cancer.

The objective of this study was to assess the impact of impaired renal function on the pharmacokinetics of tomopenem (RO4908463/CS-023), a novel carbapenem antibiotic, and its major metabolite in humans. Thirtytwo subjects were enrolled in an open-label, two-center study. Subjects were evenly assigned to one of four groups, based on creatinine clearance ranges of >80, 50 to 79, 30 to 49, and <30 ml/min. The drug was given as a single 1,500-mg constant-rate intravenous infusion over 60 min. There were no safety concerns with increasing renal dysfunction. Renal impairment had a significant impact on exposure of both tomopenem and its metabolite. Mean (؎ standard deviation) areas under the curve for tomopenem increased with decreasing renal function, from 191 ؎ 35.2 to 1,037 ؎ 238 g ⅐ h/ml. The maximum concentration of drug in plasma (C max ) increased with a maximum difference of 44% between the severe and normal groups. In contrast, the corresponding increase in C max of the metabolite was much higher, at 174%. Total body clearance was linearly correlated with creatinine clearance (R 2 ‫؍‬ 0.97; P < 0.0001). Renal clearance for tomopenem decreased with increasing severity of disease, with mean values decreasing from 4.63 ؎ 0.89 to 0.59 ؎ 0.19 liters/h. The results of this study indicated a strong correlation between the creatinine clearance and total clearance of tomopenem. While renal impairment appeared to have a significant effect on the pharmacokinetics of tomopenem, an even greater effect was seen on the elimination of the inactive metabolite.

No abstract