Model-Based Determination of Effective Blood Concentrations of @entity205 for Neutrophil Response in the Treatment of Severe @entity2150 in XXXX .

@entity1 @entity9472 @entity2150 @entity1503 @entity205
UNASSIGNED: Optimal immunosuppressive therapy in acquired @entity2150 ( @entity2150 ) remains to be refined, especially @entity205 ( @entity9472 ) use. Current recommendations state that @entity9472 @entity1503 ( @entity1503 ) should be maintained between 200 and 400  ng/mL despite the lack of supporting data. This study aimed at quantifying relationships between @entity9472 exposure and neutrophil response and determining an effective range for @entity9472 @entity1503 . Twenty-three @entity2150 @entity1 treated with @entity9472 were retrospectively analyzed. Nonlinear mixed effect modeling approaches were used to develop a pharmacokinetic-pharmacodynamic model. The pharmacokinetic model described the relationships between @entity9472 doses and @entity1503 . The pharmacodynamic model allowed to estimate boundaries for optimal @entity9472 effects, neutrophils being used as biomarker of response. A time-to-event model linked effective concentration to time-to-therapeutic success. @entity9472 @entity1503 were adequately described by a two-compartment model with first-order absorption, a lag time, and a linear elimination. The efficient range of @entity9472 @entity1503 was estimated between 87 and 120  ng/mL. Model-based simulations and external validation in three additional @entity1 confirmed these results. This original modeling approach was successful in describing the relationship between @entity9472 @entity1503 and neutrophil response in @entity2150 @entity1 . Although further evaluation of the model is necessary, this work suggests that an optimal @entity9472 @entity1503 target of 100  ng/mL would be associated with a better neutrophil response in @entity1 with @entity2150 .
