NPDE for parent and metabolite data

Dear group, Yet another question to the group. I am working on a model for drug molecule with parent-metabolite data. I am requesting NPDE in NONMEM 7.2 and plotting NPDE overlaid on standard normal distribution to see the goodness-of-fit. Now, do I need to plot different plots for parent and metabolite for such plots as with other diagnostic plots? Also, how the decorrelation is handled when two analytes within an individual are given? Regards, Ayyappa

Dear Ayyappa, My reading of the methodology is that NPDE are independent standard normally distributed regardless of design groups, so there is no problem in plotting NPDE with and without strata since they just become different diagnostics. There will be some overlapping information, e.g., if you see good fits separately by parent/metabolite, you should also see good fits jointly. Decorrelation is handled by simulations that should not interfere with the number of analytes, see Brendel K, Comets E, Laffont C, Laveille C, Mentre F (2006) Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide. Pharm Res 23(9):2036-2049. Presumably NONMEM 7.2 implementation is the same, so there should be no reason to worry. Regards, Chuanpu ~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~* Chuanpu Hu, Ph.D. Scientific Director Pharmacokinetics and Pharmacometrics Biologics Clinical Pharmacology Janssen Pharmaceutical Companies of Johnson & Johnson 1400 McKean Road, PO Box 776, Spring House, PA 19477 Phone: 215-793-7288 Fax: 215-986-1013 E-mail: [email protected] <mailto:[email protected]> ~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*~*