BACKGROUND: A pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis to build a dosing strategy for biapenem in adult patients has not been conducted. METHODS: A total of 321 plasma concentration samples from 68 adult patients (1-6 samples per patient) were assayed biologically and chromatographically, and used for a population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (40% of the time above the minimum inhibitory concentration). RESULTS: The population PK model was based on the standard two-compartment model, and creatinine clearance (Cl(cr)) was the most significant covariate that affected the drug clearance. The Monte Carlo simulation demonstrated that the dosages up to 600 mg Q12H (0.5-h infusions) achieved a PK-PD target attainment probability of > or =90%, which varied with Cl(cr) of the patient and susceptibility of the tested bacterium; however, higher dosage with prolonged infusion time (600 mg Q8H, 3 h infusion) was required for a high probability against Pseudomonas aeruginosa and Haemophilus influenzae isolates in the case of Cl(cr) = 90 ml/min. CONCLUSION: These results provide guidance for constructing a PK-PD-based strategy for tailoring biapenem regimens in adult patients. 2008 S. Karger AG, Basel.
BACKGROUND: A pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis to build a dosing strategy for biapenem in adult patients has not been conducted. METHODS: A total of 321 plasma concentration samples from 68 adult patients (1-6 samples per patient) were assayed biologically and chromatographically, and used for a population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (40% of the time above the minimum inhibitory concentration). RESULTS: The population PK model was based on the standard two-compartment model, and creatinine clearance (Cl(cr)) was the most significant covariate that affected the drug clearance. The Monte Carlo simulation demonstrated that the dosages up to 600 mg Q12H (0.5-h infusions) achieved a PK-PD target attainment probability of > or =90%, which varied with Cl(cr) of the patient and susceptibility of the tested bacterium; however, higher dosage with prolonged infusion time (600 mg Q8H, 3 h infusion) was required for a high probability against Pseudomonas aeruginosa and Haemophilus influenzae isolates in the case of Cl(cr) = 90 ml/min. CONCLUSION: These results provide guidance for constructing a PK-PD-based strategy for tailoring biapenem regimens in adult patients. 2008 S. Karger AG, Basel.
Authors: Amit Kaushik; Nicole C Ammerman; Rokeya Tasneen; Elizabeth Story-Roller; Kelly E Dooley; Susan E Dorman; Eric L Nuermberger; Gyanu Lamichhane Journal: J Antimicrob Chemother Date: 2017-08-01 Impact factor: 5.790