2. Methods
2.1 Search Strategy
PopPK studies of posaconazole from inception to May 2022 were searched
from PubMed and EMBASE databases using the following keywords:
‘posaconazole’ in title or abstract, ‘population pharmacokinetic’,
‘popPK’, ‘pop PK’, ‘PPK’, ‘population pk model’, ‘compartmental
pharmacokinetic’, ‘pharmacokinetic
model’, ‘population model’, ‘NONMEM’, ‘nonlinear mixed effects
modeling’, ‘NLME’, ‘mixed effect’, ‘WinNonmix’, and ‘Monolix’.
2.2 Inclusion/Exclusion
Criteria
All literature articles describing the PopPK models of posaconazole were
included according to the retrieval results. Studies that met the
following criteria were included in this review: (1) the study
population was human, whether adult or pediatric patients or healthy
volunteers; (2) posaconazole was used as the research drug, with no
limitation on the type of formulation; and (3) the PK analysis was
carried out and a PopPK model was established. The following studies
were excluded: (1) reviews, case reports, methodological articles, and
in vitro studies; (2) non-English language publications; (3) papers that
lack a source for details of methods or results; (4) studies using
non-compartmental or non-parametric methods.
2.3 Data Extraction
The following information was extracted from the PopPK models that met
inclusion and exclusion criteria: (1) population characteristics, such
as country, sex, weight, age, disease, administration route, dose and
posaconazole concentration; (2) model characteristics, such as the
number of samples collected, the method of modeling, evaluation, and
dose simulation; (3) Results of PopPK analysis, such as structural
models, statistical models (inter-individual and residual variation),
parameter estimates, and covariates examined and retained.
2.4 Comparison of Studies
The population characteristics, modeling strategies, and model
information for each study have been summarized in tabular form. The
steady-state concentration-time profiles of posaconazole at different
covariate levels were simulated. The daily dose of 300-600 mg was set as
the instructions. For categorical covariates, 0 and 1 represented the
absence or presence, respectively. Continuous covariates were simulated
with three levels: adult weight (60, 120, and 180 kg), child weight (10,
20, and 30 kg); age (20, 40, and 60 years); and total protein (4.8, 6.5,
and 7.8 g/dL).
The effect of different dosing regimens on posaconazole steady-state
concentration profile was also simulated. The dosage for oral
suspensions was set at 200, 300, and 400 mg thrice daily. A loading dose
of 200, 300, and 400 mg twice on the first day and a maintenance dose of
200, 300, and 400 mg once daily was set for tablets and intravenous
formulations. The infusion time of the intravenous formulations was set
at 90 min.