Integrated pharmacokinetic-pharmacodynamic modeling and allometric scaling for optimizing the dosage regimen of the monoclonal ior EGF/r3 antibody. Export

@article{citeulike:3428746, abstract = {The multiple-dose strategy with the monoclonal ior EGF/r3 antibody, in xenograft bearing nude mice, was supported upon the basis of its integrated pharmacokinetic-pharmacodynamic relationship, according to both the temporal (K(e0)=0.0015+/-0.000035h(-1)) and the time-independent sensitivity (C(50\%)(ss), 9.23+/-0.17microg/ml; C(max,eff)(ss), 12.5microg/ml) components of its tumor growth delay action. This relationship was consistent with a sigmoidal E(max) pharmacodynamic model postulating a hypothetical effect compartment that permits us to estimate an effective steady-state concentration range (7.5-12microg/ml). Using this information we calculated both the cumulative and non-cumulative dosage regimens to compare their response patterns with respect to the control group. It follows that the differences in the estimated tumor growth inhibition ratio were statistically significant between the control group and either of the treated ones (P<0.05). The median survival time in treated mice under non-cumulative regimen (72+/-10 days), predicted an increase in this parameter as compared to the control one (55+/-6 days). Finally, using the allometric paradigm, the empiric power equation for dose scaling across mammalian species allowed the calculation of the dosage schedule for further clinical trial. The estimated maintenance dose in human (70kg) was 200mg/m(2) to be given weekly, and the corresponding loading dose was 600mg/m(2).}, author = {Duconge, J. and Castillo, R. and Crombet, T. and Alvarez, D. and Matheu, J. and Vecino, G. and Alonso, K. and Beausoleil, I. and Valenzuela, C. and Becquer, M. A. and Fern\'{a}ndez-S\'{a}nchez, E.}, citeulike-article-id = {3428746}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/14757498}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=14757498}, issn = {0928-0987}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, keywords = {allometric\_scaling, antibody, pharmacokinetics}, month = {February}, number = {2-3}, pages = {261--270}, posted-at = {2008-10-19 10:35:42}, priority = {2}, title = {Integrated pharmacokinetic-pharmacodynamic modeling and allometric scaling for optimizing the dosage regimen of the monoclonal ior EGF/r3 antibody.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14757498}, volume = {21}, year = {2004} }

TY - JOUR ID - citeulike:3428746 L3 - citeulike-article-id:3428746 N2 - The multiple-dose strategy with the monoclonal ior EGF/r3 antibody, in xenograft bearing nude mice, was supported upon the basis of its integrated pharmacokinetic-pharmacodynamic relationship, according to both the temporal (K(e0)=0.0015+/-0.000035h(-1)) and the time-independent sensitivity (C(50%)(ss), 9.23+/-0.17microg/ml; C(max,eff)(ss), 12.5microg/ml) components of its tumor growth delay action. This relationship was consistent with a sigmoidal E(max) pharmacodynamic model postulating a hypothetical effect compartment that permits us to estimate an effective steady-state concentration range (7.5-12microg/ml). Using this information we calculated both the cumulative and non-cumulative dosage regimens to compare their response patterns with respect to the control group. It follows that the differences in the estimated tumor growth inhibition ratio were statistically significant between the control group and either of the treated ones (P<0.05). The median survival time in treated mice under non-cumulative regimen (72+/-10 days), predicted an increase in this parameter as compared to the control one (55+/-6 days). Finally, using the allometric paradigm, the empiric power equation for dose scaling across mammalian species allowed the calculation of the dosage schedule for further clinical trial. The estimated maintenance dose in human (70kg) was 200mg/m(2) to be given weekly, and the corresponding loading dose was 600mg/m(2). IS - 2-3 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences SN - 0928-0987 EP - 270 TI - Integrated pharmacokinetic-pharmacodynamic modeling and allometric scaling for optimizing the dosage regimen of the monoclonal ior EGF/r3 antibody. VL - 21 SP - 261 KW - allometric_scaling KW - antibody KW - pharmacokinetics AU - Duconge, J AU - Castillo, R AU - Crombet, T AU - Alvarez, D AU - Matheu, J AU - Vecino, G AU - Alonso, K AU - Beausoleil, I AU - Valenzuela, C AU - Becquer, MA AU - Fernández-Sánchez, E PY - 2004/02// UR - http://view.ncbi.nlm.nih.gov/pubmed/14757498 ER -