Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease.

ABSTRACT

PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of ß-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population. METHODS: In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study. RESULTS: On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06-103.18 L), terminal half-life (T1/2) (4.51; 2.67-8.88 h) and decreased clearance (6.52; 4.43-10.16 L/h) have been shown. CONCLUSION: In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target. RETROSPECTIVELY REGISTERED The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5.