Universität zu Köln

Li, Xia, Zoller, Michael, Fuhr, Uwe, Huseyn-Zada, Mikayil, Maier, Barbara, Vogeser, Michael, Zander, Johannes and Taubert, Max ORCID: 0000-0001-8925-7782 (2019). Ciprofloxacin in critically ill subjects: considering hepatic function, age and sex to choose the optimal dose. J. Antimicrob. Chemother., 74 (3). S. 682 - 691. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Background Pathophysiological changes often result in altered pharmacokinetics of ciprofloxacin in critically ill patients. Although ciprofloxacin clearance (CLCIP) substantially depends on kidney function in healthy volunteers, its relationship to measured creatinine clearance (CLCRM) is weak in critically ill patients. Objectives To assess the need for dose reductions in isolated or combined kidney and liver dysfunction in critically ill patients and to re-evaluate relationships between kidney parameters, demographics and ciprofloxacin pharmacokinetics. Methods A population pharmacokinetic model was developed based on 444 ciprofloxacin serum concentrations from 15 critically ill patients with severe infections. CLCIP relationships to parameters reflecting hepatic function, CLCRM, Cockcroft-Gault creatinine clearance (CLCRCG), serum creatinine, sex, weight and age were explored. A simulation study was conducted to integrate knowledge from the new and previously published models. Results Total bilirubin was identified as a hepatic parameter with a clear relationship to CLCIP. A significant relationship between CLCIP and CLCRCG could be attributed to age and sex only. CLCIP was not associated with CLCRM. The predicted risk of potential overexposure (AUC>250mg<bold>h</bold>/L) was low even with 1200mg/day ciprofloxacin daily for patients with reduced CLCRCG (<30mL/min: risk of 0.7%), while the risk was remarkably higher in elderly female patients with elevated bilirubin (risk of about 20% for 65-year-old women with total bilirubin of 4mg/dL). Conclusions Bilirubin, age and sex should be considered to assess the need for dose reductions. For MICs 0.25mg/L, it might be appropriate to reduce the dose to 400mg/day for elderly female subjects with high bilirubin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Li, Xia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zoller, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Huseyn-Zada, Mikayil UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogeser, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-154968
DOI:	10.1093/jac/dky485
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	74
Number:	3
Page Range:	S. 682 - 691
Date:	2019
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAVENOUS CIPROFLOXACIN; DRUG-METABOLISM; PHARMACOKINETICS; CREATININE; SERUM; DISEASE; MODEL; EQUATIONS Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15496