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[NMusers] Is it possible that IIV (%CV) of final model was higher than IIV of base model?

From: Vichapat Tharanon <>
Date: Mon, 8 Jul 2019 21:21:12 +0700

Dear All,

            I am a hospital pharmacist and I am working on NONMEM as a new
user. I have modeled the oral immediate-released tacrolimus (Prograf) in
adult liver transplant patients.

Most of the data were trough concentration (about 1170 levels) from routine
monitoring tacrolimus data in the period of first day post-transplantation
to 6 months. The model was constructed by NONMEM 7.2 using FOCE INTERACTION
methods with the subroutines ADVAN2 TRANS2 (one compartment model with
linear absorption and elimination). The ka could not be estimated and then
was fixed at 4.48 h-1. The IIIV and RUV were described by exponential and
additive error model, respectively. Forward addition of a liver enzyme (ALT
), Hemoglobin and total bilirubin (TB) on CL/F reduced OFV significantly (delta
OFV ~98, 42, 28, respectively) but IIV of CL/F was increased from 37.2% to
38.1%. It was found that no significant covariates influenced to V/F but
IIV of V/F was also increased from 55% to 63%. Residual variability was
reduced from a SD of 2.80 to 2.65, when compared final model and base model.

            I feel uncomfortable with these findings. Is it possible that
IIV of CL/F and V/F were rising after adding the significant covariates
whereas %RSE of the CL/F and V/F estimate as well as IIV of CL/F and IIV of
V/F in final model were slightly decreasing. May I have your comment or
suggestion; I would really appreciate it. Thank you in advance.

Best regards,


Received on Mon Jul 08 2019 - 10:21:12 EDT

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