Population Pharmacokinetics Model Repository for Caspofungin: a
Caspofungin is an echinocandin antifungal commonly used as the
first-line therapy for invasive candidiasis, salvage therapy for
invasive aspergillosis. Pharmacokinetic variabilities and suboptimal
exposure have been reported for caspofungin, increasing the risk of
insufficient efficacy. We aimed to consolidate information from
population pharmacokinetic studies, compare model performance, identify
significant covariates affecting caspofungin’s PKs, evaluate probability
of target attainment in different studies and assemble
pharmacokinetic/pharmacodynamic target to address existing knowledge
gaps that may warrant further investigation in future. We performed a
systematic search strategy to review the PPK studies of caspofungin.
Four databases were searched. We extracted information for the
comparison of models, evaluation of the impact of covariates on
clearance and apparent volume and the calculation of probability of
target attainment under specific minimum inhibitory concentration.
Thirteen studies were included. The simulation results showed that under
labeled dose, pediatrics exhibited notably higher exposure than adults.
Body size was the most identified covariate that affected both clearance
and volume of distribution. For C. albicans and C. parapsilosis, none of
the populations achieved a PTA of ≥ 90%. In contrast, for C. glabrata,
70% of the adult patients reached a PTA of ≥ 90%, while all pediatric
patients achieved the same PTA level. At the recommended dosage, adults
showed lower exposure to caspofungin compared to pediatrics. It is
crucial to consider body size, liver function and serum albumin when
determining caspofungin dosage regimens. Furthermore, further research
is required to comprehensively understand the pharmacokinetics of
caspofungin in pediatrics.