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Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients
Author(s) -
Kees Martin G.,
Minichmayr Iris K.,
Moritz Stefan,
Beck Stefanie,
Wicha Sebastian G.,
Kees Frieder,
Kloft Charlotte,
Steinke Thomas
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.600
Subject(s) - meropenem , renal function , cystatin c , pharmacokinetics , nonmem , creatinine , medicine , dosing , pharmacodynamics , population , urology , renal replacement therapy , pharmacology , chemistry , antibiotics , biochemistry , environmental health , antibiotic resistance
Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady‐state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21‐85 years, body weight 55‐125 kg, APACHE II 5‐29, measured creatinine clearance 22.7‐297 mL/min). Urine was collected for the quantification of renal clearance of meropenem and creatinine. Cystatin C was measured as an additional marker of renal function. Population pharmacokinetic models were developed using NONMEM ® , which described total meropenem clearance and its relationship with several estimates of renal function (measured creatinine clearance CL CR , Cockcroft‐Gault formula CL CG , Hoek formula, 1/plasma creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate of renal function improved the model performance. The strongest association of clearance was found with CL CR (typical clearance = 11.3 L/h × [1 + 0.00932 × (CL CR – 80 mL/min)]), followed by 1/plasma cystatin C; CL CG was the least predictive covariate. Neither age, weight, nor sex was found to be significant. These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion. The covariate CL CR offers the best predictive performance; if not available, cystatin C may provide a promising alternative to plasma creatinine.