Funaki Tomoo, Shiomi Mari
Nippon Roche K.K. 6-1, Shiba 2-chome, Minato-ku,Tokyo, 105-8532 Japan
Nonlinear Mixed-Effects Methods for S-PLUS (mixed-effects modeling function – version 3.3 NLME) have been reported. A zero-order infusion model was created for NLME in this study. The data from the literature for trastuzumab were used for analysis with the zero-order infusion model for NLME; data for single as well as multiple dosing (1 q per week) studies were available for doses of 1, 2, 4 and 8 mg/kg. The two-compartment model was slightly better than the one-compartment model in describing the disposition of trastuzumab, for both single and multiple dosing. In single-dose fitting, the predicted concentrations agreed well with the observed concentrations in the one-compartment model as well as the two-compartment model. However, in the multiple-dose fitting, the predicted concentrations slightly underestimated the observed concentrations at higher doses; this was considered evidence of the nonlinear pharmacokinetics of trastuzumab. Using the pharmacokinetic parameters obtained in NLME analysis, the serum levels with a loading dose of 8 mg/kg and maintenance dose of 6 mg/kg once per 3 weeks were simulated for 50 subjects. Simulated levels were lower than the observed concentrations for 8 mg/kg multiple dosing. These findings suggest that the 8/6 mg once per 3 weeks regimen is as safe pharmacokinetically as 8 mg/kg per week multiple dosing.
Reference: PAGE 10 (2001) Abstr 187 [www.page-meeting.org/?abstract=187]
Poster: poster