Re: Nagaraja

Date: Fri, 11 Jun 1999 14:27:21 +0200 From: Pascal Girard <pg@upcl.univ-lyon1.fr> Subject: Re: Nagaraja Thank you Mats for remembering us about Taright's work presented at PAGE97! One of my fellow here in Lyon is modelling pop PK of Tacrolimus in liver transplanted patients. Preliminary results will be presented at PAGE next week. Other very recent and not definitive results we have (not shown on next week poster) indicate that inclusion in the CL submodel of hematocrit or hepactic markers as transaminase, using a step function to interpolate the covariate -just as suggested by Lewis- and a multiplicative model, dramatically reduces the NONMEM objective function (-170 just for transaminase and -187 for transa & HEM). Graphics also indicate much better goodness of fit. However what I am puzzled about is the fact that, when introducing these time varying covariates, interindividual variability on CL and V is slightly increased, and intraindividual variability is decreased for the only additive term of error model (which is additive and multiplicative - I also have to say that most concentrations are through levels). Has anyone experienced this situation? Any comments on this? Cheers, Pascal Girard ------------------------------------------------------------------ Service Pharmacologie Clinique PG@upcl.univ-lyon1.fr Faculte RTH Laennec Tel : +33 (0)4 78 78 57 26 BP 8071, rue Guillaume Paradin Fax : +33 (0)4 78 77 69 17 69376 LYON Cedex 08 FRANCE http://www.spc.univ-lyon1.fr