Cefoperazone/sulbactam therapeutic drug monitoring in patients with liver cirrhosis: Potential factors affecting the pharmacokinetic/pharmacodynamic target attainment

Autor:	Tao Zhang, Ying Zhang, Yaling Dong, Yuzhu Dong, Li Zhu, Taotao Wang, Ying Li
Rok vydání:	2019
Předmět:	Adult Liver Cirrhosis Male medicine.medical_specialty Cirrhosis Cefoperazone Renal function Toxicology 030226 pharmacology & pharmacy Gastroenterology Young Adult 03 medical and health sciences Cmin 0302 clinical medicine Pharmacokinetics Internal medicine polycyclic compounds Humans Medicine Aged Retrospective Studies Aged 80 and over Pharmacology Dose-Response Relationship Drug medicine.diagnostic_test business.industry Bacterial Infections General Medicine Sulbactam Middle Aged medicine.disease Anti-Bacterial Agents Drug Combinations Treatment Outcome Therapeutic drug monitoring Pharmacodynamics Female Drug Monitoring business 030217 neurology & neurosurgery medicine.drug
Zdroj:	Basic & Clinical Pharmacology & Toxicology. 125:353-359
ISSN:	1742-7843 1742-7835
Popis:	Objectives Cefoperazone/sulbactam trough concentration (Cmin ) varies widely in cirrhotic patients. The objective of this study was to describe the characteristics of Cmin and to identify factors associated with the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of cefoperazone/sulbactam in cirrhotic patients. Methods Data were collected retrospectively from cirrhotic patients who received cefoperazone/sulbactam treatment. The Cmin was measured using a validated liquid chromatography-tandem mass spectrometry. The PK/PD target of 100% fT > MIC was used for cefoperazone/sulbactam. Multivariate logistic regression and classification and regression tree (CART) analysis were performed to identify the factors affecting the PK/PD target attainment in these patients. Results Cefoperazone and sulbactam Cmin were measured simultaneously in 103 plasma samples from 70 cirrhotic patients. Cefoperazone and sulbactam Cmin were 89.27 ± 44.38 mg/L and 10.09 ± 13.01 mg/L, respectively. The PK/PD target of 100% fT > MIC was achieved in 47.1% (33/70) patients for cefoperazone and in 28.6% (20/70) patients for sulbactam. The CART analysis revealed that cefoperazone Cmin was likely to reach the PK/PD target in patients with serum bilirubin levels between 26.15 μmol/L and 99.15 μmol/L. Inversely, lower cefoperazone Cmin was observed in patients with bilirubin levels ≤26.15 μmol/L and serum albumin >38.45 g/L or in patients with bilirubin levels >99.15 μmol/L and creatinine clearance (CrCl) >139.13 mL/min. Additionally, patients had higher sulbactam Cmin when CrCl was below 62.85 mL/min. Conclusions This study shows that current cefoperazone/sulbactam dosage regimens may result in inadequate plasma concentrations in cirrhotic patients. We recommend monitoring the Cmin of cefoperazone/sulbactam to ensure efficacy of cefoperazone/sulbactam treatment.
Databáze:	OpenAIRE
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