estimating Ka from dataset combining rich sample study and sparse sampling study

From: Ethan Wu Date: June 17, 2009 technical Source: mail-archive.com
Dear all, I am working on this pop PK analysis. the objective is, to explore some covariates on the exposure. the dataset has rich sampled study, with absorption phase well captured. and also sparse sampling study with only trough sample, and another sample around 1-2hr after dosing with rich sample study data, the ka and eta on Ka is well estimated using FOCE INT method and 1ct 1st order model. but when with pooled dataset, using the same model and method, eta on Ka is estimated to be almost 0, the fit to the data from rich sampled study became little worse on the peak. Is there way to keep a good estimation of Eta on Ka, which is to make sure the good capture of Cmax, at least for rich sampled subjects? with my limited knowledge, I was thinking: -- fixing Eta on ka with the estimate from rich sample study alone -- hybrid estimating methods -- nonparametric method Any comments will be highly appreciated.