The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia

Thumbnail Image
Date
2019-04-09
Authors
Stachowiak, Anna
Szałek, Edyta
Karbownik, Agnieszka
Łojko, Anna
Porażka, Joanna
Przewoźna, Iwona
Grabowski, Tomasz
Wolc, Anna
Grześkowiak, Edmund
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
Authors
Person
Wolc, Anna
Affiliate Assistant Professor
Research Projects
Organizational Units
Organizational Unit
Journal Issue
Is Version Of
Versions
Series
Department
Animal Science
Abstract

Background and Objectives Numerous studies have confirmed the influence of diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is chiefly metabolised by glucuronidation and sulphation. This study assessed the influence of diabetes on the pharmacokinetics of paracetamol and its metabolites: glucuronide (APAP-glu) and sulfate (APAP-sulfate) in FN patients.

Methods Patients with FN received single intravenous dose 1000 mg of APAP. The FN patients were allocated to one of two groups: diabetics (DG, n = 7) or non-diabetics (NDG, n = 11). The plasma concentrations of paracetamol and its metabolites were measured with the validated high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection.

Results Pharmacokinetic parameters (mean [SD]) of APAP in the DG and NDG groups were as follows: Cmax (maximum comcentration) = 21.50 [11.23] vs. 23.42 [9.79] mg/L, AUC 0–t (area under the concentration–time curve) = 44.23 [17.93] vs. 41.43 [14.57] mg·h/L, t1/2kel (elimination half-life) = 2.28 [0.80] vs. 2.11 [0.80] h. In both groups the exposure to APAP was comparable. The study did not reveal differences between the two groups in the pharmacokinetics of APAP-glu and APAP-sulfate. The Cmax and AUC 0–t ratio between the metabolites and APAP were similar.

Conclusions No differences in the pharmacokinetics of APAP, APAP-glu and APAP-sulfate in patients with FN indicates that diabetes does not influence glucuronidation and sulfatation of paracetamol.

Comments

This article is published as Stachowiak, A., Szałek, E., Karbownik, A. et al. The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia. Eur J Drug Metab Pharmacokinet 44, 289–294 (2019). doi: 10.1007/s13318-018-0508-4.

Description
Keywords
Citation
DOI
Copyright
Mon Jan 01 00:00:00 UTC 2018
Collections