2.4 Study Comparison
We developed virtual patients with different age: infants (10 kg,
1-year-old) taking 300 mg OXC every 12 h (q12h), children (30 kg, 10
years old) taking 300 mg OXC q12h, and adults (70 kg, 40 years old)
taking 600 mg OXC q12h. The concentration–time profiles in virtual
patients were drew on the basis of the restored PPK model and study
population in each included study. They received multiple doses of OXC
alone and achieve stable state. The sex of the virtual patient was
selected as male.
The identified covariates effect on clearance (CL) in the included
studies was analysed and showed by a forest map. The CL change less than
between 80%-125% was not considered to have a significant clinical
correlation [19]. For binary covariates such as co-administration
with medications, we use 0 for monotherapy and 1 for co-administration
with medications. For continuous covariates that were included in only
one model, we used the same range values as the study. For continuous
covariates included in multiple studies, we scaled them to the same
range for comparison. The effect of each covariate on CL was shown as
the ratio of CL in the range of the covariate divided by the typical CL
value in each study.
The simulation was conducted using NONMEM (version 7.4; ICON Development
Solutions, Ellicott City, MD, USA) software. R (version 3.5.1;
http://www.r-project.org/) was used to generate the concentration–time
plots and forest plots.