(B) In vivo tumor growth kinetics using A431 xenograft mouse model with dose titration of a CD3-EGFR DVD-Ig molecule (1 mpk, 4 mpk, or 13 mpk) with or without the addition of CD3-positive human T-cells.
Aylward et al. (2005) and Emond et al. (2005) suggest that using a pharmacokinetic model with dose-dependent elimination results in nonlinear relationships between measured body burdens and predicted peak body burdens.
However, a dose effect or drug exposure effect could replace the shrinkage parameter (SR), and Stein et al. [ 22] have applied a model with dose-dependent exponential tumour shrinkage and linear tumour growth to tumour SLD data from metastatic RCC patients treated with everolimus.
Time to infection with intestinal geohelminths was estimated using Kaplan Meier analyses to evaluate infection-free status within each treatment group and the relative risk (RR) calculated using a Cox's regression model with dosing schedule and pooled centre as covariates.
As Nec-1s is a potent inhibitor of RIPK1 and cellular necroptosis while lacking IDO inhibitory activity, we tested it in the TNF-induced SIRS model with doses that were protective (Hi: 6 mg/kg) and sensitizing for Nec-1 (Lo: 0.6 mg/kg).
A number of in vivo studies by us and others in Lewis lung cancer allograft [ 14] and PCa xenograft [ 7, 13] models with a dose of 20 or 25 mg/kg every other day have shown anti-cancer efficacy without adverse effect on body weight.
The most active compound 4g effectively suppressed seizure effect in both the animal models with median doses of 15.6 mg/kg (MES ED50), 278.4 mg/kg (scPTZ ED50) and 534.4 mg/kg (TD50) with no sign of neurotoxicity.
When we evaluated curvature by adding quadratic dose to a model with continuous dose, there was some evidence for concavity that is, downward curvature (P=0.009 for quadratic term).
The analysis incorporated a dose-response assessment by considering low dose pioglitazone (15 mg), high dose pioglitazone (30 mg and 45 mg), low dose rosiglitazone (2 mg and 4 mg), and high dose rosiglitazone (8 mg) as time dependent covariates in the regression model, with high dose rosiglitazone as the reference group.
The less-than-proportional increase in nitrite and nitrate exposure at higher nitrite doses is modeled with a dose-dependent increase in clearance.
