Ceftazidime-avibactam (CAZ-AVI) pharmacokinetics in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF).

Autor: O'Jeanson A; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Ioannidis K; Clinical pharmacist, Hygeia General Hospital, Athens, Greece., Nielsen EI; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Galani L; 1(st) Department of Internal Medicine & Infectious Diseases, Hygeia General Hospital, Athens, Greece., Ginosyan A; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Paskalis H; ICU, Hygeia General Hospital, Athens, Greece., Loryan I; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Giamarellou H; 1(st) Department of Internal Medicine & Infectious Diseases, Hygeia General Hospital, Athens, Greece., Friberg LE; Department of Pharmacy, Uppsala University, Uppsala, Sweden. Electronic address: lena.friberg@farmaci.uu.se., Karaiskos I; 1(st) Department of Internal Medicine & Infectious Diseases, Hygeia General Hospital, Athens, Greece.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2025 Jan; Vol. 65 (1), pp. 107394. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1016/j.ijantimicag.2024.107394
Abstrakt: Purpose: To investigate the pharmacokinetics (PK) of ceftazidime-avibactam (CAZ-AVI) in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF), and compare with a general phase III trial population.
Methods: A prospective PK study was conducted in critically ill patients who received CVVHDF for acute kidney injury, treated with CAZ-AVI (1000/250 mg or 2000/500 mg q8h). Plasma and CVVHDF-circuit samples were collected to determine CAZ-AVI concentrations. Individual PK parameters at steady-state were estimated using non-compartmental analysis. For visual comparison, plasma concentrations from CVVHDF patients were overlaid with simulated data from patients not receiving CVVHDF based on previously developed population PK models.
Results: A total of 35 plasma samples and 16 CVVHDF-circuit samples were obtained from four patients, with two patients sampled on two separate occasions. Median total clearance and volume of distribution were 4.54 L/h and 73.2 L for CAZ and 10.5 L/h and 102 L for AVI, respectively. Median contribution of CVVHDF to total clearance was 19.8% for CAZ and 5.3% for AVI. Observed CAZ-AVI PK profiles were generally within the 90% confidence interval of model predictions, but the observed concentrations were notably lower early (0-2 h) and higher later (4-8 h) in the dosing interval, suggesting a higher volume of distribution.
Conclusions: These results suggest that the CAZ-AVI dose regimens used in this study can be applicable in critically ill patients undergoing CVVHDF, despite the different shape of the PK profiles observed in this population. Further research with a larger patient cohort is warranted to validate and refine these findings.
Competing Interests: Declaration of competing interest H.G. has received speaker honoraria from Pfizer and MSD. I.K. has received speaker honoraria from Pfizer. Menarini and bioMérieux. All other authors declare no conflict of interest.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: