Population Pharmacokinetics and Dosing Regimen Optimization of Ceftazidime in Plasma and Cerebrospinal Fluid of Neonatal Sepsis Patients
Description
The study included 69 neonates with sepsis.Based on plasma and cerebrospinal CSF concentration data collected from neonates with sepsis, statistical and graphical methods were employed to evaluate the stability and predictive performance of the model.The pharmacokinetic/pharmacodynamic (PK/PD) target for clinical efficacy was defined as the duration of free drug concentration above the minimum inhibitory concentration (MIC) for ≥70% of the dosing interval (70% fT>MIC). Monte Carlo simulations were performed to identify optimal dosing regimens achieving a target attainment probability (PTA) ≥90%.Demographic and laboratory parameters were documented, including sex, body weight, height, body surface area (BSA), gestational age(GA), postnatal age(PNA), postmenstrual age(PMA), and biochemical markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), γ-glutamyl transferase (γ-GT), albumin, globulin, uric acid (UA), blood urea nitrogen (BUN), serum cystatin C (Cys-C), and serum creatinine (SCr). Estimated glomerular filtration rate (eGFR) was calculated using the modified Schwartz formula, where eGFR (mL/min/1.73 m²) = (k × height) / SCr, with k = 0.33 for preterm infants and k = 0.45 for term infants. plasma creatinine was measured using the Roche cobas 8000 c702 enzymatic assay. Additionally, CSF analysis included protein, glucose, and chloride levels.