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Abstract

Background:For the treatment of peritoneal dialysis-associated peritonitis (PDAP), ceftazidime is routinely admixedwith peritoneal dialysis (PD) solutions before its intraperitoneal administration. One of the major degradation productsof ceftazidime is pyridine, a potentially toxic compound. Depending on the type of PD solution, ceftazidime is exposedto an environment with acidic or basic pH, and depending on the type of dosing and individual unit practices related topreparation and storage, ceftazidime can be at body temperature for 4–10 h, resulting in potentially varying rates ofdegradation to pyridine by-product. No study has investigated whether the amount of generated pyridine exceeds themaximum daily exposure limit of 2 mg when ceftazidime-PD admixtures are kept at body temperature. Therefore, thecurrent study aimed to determine the levels of pyridine generated in PD-ceftazidime admixtures kept at 37C forvarious time points.Methods: was admixed with 2 L Dianeal (1.5%, 2.5% and 4.25% dextrose) and 2 L Physioneal (1.36%, 2.27%and 3.86% glucose) PD solutions to obtain a concentration of 125 mg/L (continuous dosing model) or 500 mg/L (intermittent dosing model). A total of 36 PD admixtures (3 bags for each type of PD solution and 3 bags for each type of dosing)were prepared and stored at 37C for 10 h. An aliquot was withdrawn at time 0 (baseline) and after 2, 6, 8 and 10 h ofstorage. The withdrawn samples were then analysed to determine the concentrations of ceftazidime and pyridine usinghigh-performance liquid chromatography.Results: With the intermittent dosing model (500 mg/L), ceftazidime was found to be stable for only 2 and 6 h whenadmixed with 3.86% and 2.27% glucose Physioneal PD solutions, respectively. While ceftazidime (500 mg/L) retained morethan 90% of its initial concentration in the three types of Dianeal and 1.36% dextrose Physioneal solutions for 10 and 8 h,respectively, the generated amount of pyridine ranged between approximately 290% and 371% more than the dailyrecommended limit. With the continuous dosing model (125 mg/L), ceftazidime was found to be stable for 6 h in all threetypes of Physioneal PD solutions, but the total amount of generated pyridine with four daily exchanges (6 h each) wasestimated to be 170–360% over the daily recommended limit. Ceftazidime (125 mg/L) was chemically stable whenadmixed with three types of Dianeal PD solutions and stored at 37C for 10 h, and the levels of pyridine were estimated tobe less than the maximum recommended daily limit.Conclusions: Until the outcomes of this in vitro study are confirmed by appropriate in vivo studies, continuousdosing of ceftzadime–Dianeal admixtures for the treatment of PDAP may be preferred over continuous dosing ofceftazidime–Physioneal admixtures, and intermittent dosing of ceftazidime–Physioneal and ceftazidime–Dianea admixtures, as ceftazidime remains stable and the generated levels of pyridine are below the maximum recommended daily exposure.

Item Type:	Article
Authors/Creators:	Nguyen, TTT and Harmanjeet, H and Wanandy, T and Castelino, R and Sud, K and Jose, M and Peterson, G and Patel, R
Keywords:	stability, ceftazidime, pyridine, HPLC, neurotoxicity
Journal or Publication Title:	Peritoneal Dialysis International
Publisher:	Multimed Inc
ISSN:	0896-8608
DOI / ID Number:	https://doi.org/10.1177/0896860819887636
Copyright Information:	Copyright 2020 The Authors
Related URLs:	UTAS Profile: Castelino, R Google Scholar: Jose, M UTAS Profile: Jose, M UTAS Profile: Peterson, G UTAS Profile: Patel, R
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