کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3377381 1219979 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pharmacokinetic–pharmacodynamic target attainment analysis of meropenem in Japanese adult patients
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Pharmacokinetic–pharmacodynamic target attainment analysis of meropenem in Japanese adult patients
چکیده انگلیسی

This study was a pharmacokinetic (PK)–pharmacodynamic (PD) target attainment analysis of meropenem in Japanese adult patients. Plasma drug concentration data (265 samples from 42 patients) were used for population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK–PD target (40% of the time above the MIC for the bacterium). The final population PK model identified creatinine clearance (Clcr, ml/min) and body weight (BW, kg) as the most significant covariates: Cl (l/h) = 0.0905 × Clcr + 2.03, Vc (l) = 0.199 × BW, Q (l/h) = 4.02, and Vp (l) = 4.55, where Cl is the clearance, Vc and Vp are the volumes of distribution of the central and peripheral compartments, respectively, and Q is the intercompartmental clearance. The Monte Carlo simulation developed the PK–PD breakpoints (the highest MIC values at which the probabilities of target attainment in plasma are 80% or more) for meropenem regimens, the values of which varied with the Clcr and BW of the patient. The simulation also demonstrated that 0.25 g every 12 h (0.5-h infusion) achieved a target attainment probability of 82.4–100% against Escherichia coli, methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae isolates. However, against Pseudomonas aeruginosa isolates, 0.5 g every 8 h or 1 g every 8 h was required to achieve 80% or more probability in most typical patients. These results provide a PK–PD-based strategy for tailoring a meropenem regimen according to Clcr and BW of a Japanese adult patient and susceptibility of the causative bacteria.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Infection and Chemotherapy - Volume 16, Issue 1, 2010, Pages 25-32