Affiliations: [a] Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA | [b] Veterans Administration Medical Center, Birmingham, AL, USA | [c] Centocor, Inc., Malvern, PA, USA
Abstract: In this study, limited sampling models for HA-1A human IgM monoclonal antibody were developed to predict the area under the concentration time curve from timed serum concentrations. Patients were administered 15 minute infusions of 25 mg (11 patients), 100 mg (15 patients), and 250 mg (2 patients). A detailed pharmacokinetic analysis (eight time points) was performed to obtain the area under the curve for each of the 28 patients using a one-compartment model with the values normalized to a dose of 100 mg. Various models were then developed to estimate the area under the curve from one and two timed concentrations using regression analysis methodology. Of these models, four were determined to be of interest with coefficients of determinations ranging from 0.92 to 0.97. They performed quite well in predicting the area under the curve values with relative root mean squared predictive error of 7.1 to 10.8% and relative mean predictive error of −4.5 to +6.9%. These models should be extremely useful in larger scale, Phase II/III studies of HA-1A in correlating the estimated area under the curve with various demographic data, toxicity, and efficacy.
