Pharmacokinetics of a mouse/human chimeric monoclonal antibody (C-17-1A) in metastatic adenocarcinoma patients.

Abstract

The pharmacokinetic characteristics of a mouse/human chimeric monoclonal antibody (C-17-1A) were determined in 10 patients with metastatic adenocarcinoma following the administration of either 10-mg or 40-mg infusions as a single or multiple dose. The administration of single 10-mg (n = 5) and 40-mg (n = 5) doses infused over 1 hr resulted in mean apparent steady-state distribution volumes of 4.13 +/- 0.97 and 5.16 +/- 1.92 liters, respectively, indicating that C-17-1A appears to distribute throughout the vascular compartment and into limited extracellular fluid volume. The disposition of C-17-1A was adequately characterized using a two-compartment open model with mean distribution half-lives of 15.8 and 18.5 hr and mean elimination half-lives of 90.0 and 97.6 hr for the 10- and 40-mg groups, respectively. A linear relationship was observed between AUC and dose (micrograms/kg). The clearance of C-17-1A was correlated linearly with total Ig, IgG, and tumor size. Multiple administration of either 10-mg (n = 3) or 40-mg (n = 3) doses of C-17-1A infused over 1 hr every 14 days for a total of three doses resulted in superimposable mean serum concentration versus time data and consistent mean pharmacokinetic characteristics. These data indicate that C-17-1A exhibits linear, nonsaturable distribution and elimination characteristics in man over the dose range studied (i.e., 130 to 880 micrograms/kg). The multiple-dose pharmacokinetics of C-17-1A were predictable, indicating a lack of an antibody response to C-17-1A over a period of 42 days.(ABSTRACT TRUNCATED AT 250 WORDS)