The appropriate approach is to fit parent compound and the metabolites simultaneously, since it can help uniquely define the PK parameters, especially the CL. As we know that CL is a lumped parameter without metabolite information. Sequential estimation is the approach when there is no better way to solve the problem in simultaneous fitting due to numerical problem.
This is different situation from PK-PD fitting. In the situation if PD has impact on PK, also, simultaneous fitting is the way to go. xiaofeng Xiaofeng Wang, PhD Oncology, Novartis (862)778-8856 (o) "Xiao, Alan" <[EMAIL PROTECTED]> Sent by: [EMAIL PROTECTED] 12/09/2008 01:30 PM To "Bachman, William" <[EMAIL PROTECTED]>, <nmusers@globomaxnm.com> cc Subject RE: [NMusers] Simultaneous vs sequential for modeling parent AND metabolites in pop PK Dear All, Thanks for your response and I'm sorry for the confusion. I'm talking about the sequential/simultaneous modeling to fit parent concentrations AND metabolites in pop PK, not about PD data at all. That is for sequential approach, you develop a model to fit the parent data first and then fix the PK parameters for parents to develop a model to fit the metabolite. While, for simultaneous approach, you develop a model to fit both parent and metabolites simultaneously (to simultaneously estimate parameters for both parent and metabolites). Alan -----Original Message----- From: Bachman, William [mailto:[EMAIL PROTECTED] Sent: Tuesday, December 09, 2008 11:26 AM To: Xiao, Alan Cc: nmusers@globomaxnm.com Subject: RE: [NMusers] Simultaneous vs sequential for modeling parent AND metabolites in pop PK The argument against the simultaneous approach is that the PD data can "drive" the PK model, particulary since the PD data usually has more variability. -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Xiao, Alan Sent: Tuesday, December 09, 2008 11:02 AM To: nmusers@globomaxnm.com Subject: [NMusers] Simultaneous vs sequential for modeling parent AND metabolites in pop PK Dear All, I know this is an old topic but would like to see the statistics. When you have to develop a pop PK model for both parent and active metabolites, which approach do you prefer or have you used most: simultaneous or sequential? Which way do you think is more scientific? I heard comments saying that the simultaneous approach is not scientific. Thanks, Alan ICON plc made the following annotations. ------------------------------------------------------------------------------ This e-mail transmission may contain confidential or legally privileged information that is intended only for the individual or entity named in the e-mail address. If you are not the intended recipient, you are hereby notified that any disclosure, copying, distribution, or reliance upon the contents of this e-mail is strictly prohibited. If you have received this e-mail transmission in error, please reply to the sender, so that ICON plc can arrange for proper delivery, and then please delete the message. Thank You, ICON plc South County Business Park Leopardstown Dublin 18 Ireland Registered number: 145835
