1. J Antimicrob Chemother. 2020 Sep 1;75(9):2650-2656. doi: 10.1093/jac/dkaa176.

Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy 
volunteers after intravenous and subcutaneous administration: a randomized 
crossover microdialysis trial.

Matzneller P(1), Ngougni Pokem P(2), Capron A(3), Lackner E(1), Wulkersdorfer 
B(1), Nussbaumer-Pröll A(4), Österreicher Z(4), Duchek M(1), Van de Velde S(5), 
Wallemacq PE(3), Mouton JW(6), Van Bambeke F(2), Zeitlinger M(1).

Author information:
(1)Department of Clinical Pharmacology, Medical University of Vienna, Austria.
(2)Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, 
Brussels, Belgium.
(3)Clinical Chemistry Department, Cliniques Universitaires St. Luc, Université 
catholique de Louvain, Brussels, Belgium.
(4)Department of Medicine 1, Division of Infectious Diseases and Tropical 
Medicine, Medical University of Vienna, Vienna, Austria.
(5)EUMEDICA S.A. Manage, Belgium.
(6)Department of Medical Microbiology and Infectious Diseases, Erasmus MC, 
Rotterdam, The Netherlands.

BACKGROUND: The antibiotic temocillin has recently been rediscovered as a 
promising therapeutic option against MDR Gram-negative bacteria. However, some 
aspects of the pharmacokinetic (PK) profile of the drug are still to be 
elucidated: subcutaneous administration of temocillin might be of interest as an 
alternative to the intravenous route in selected patients. Similarly, 
information on the penetration of temocillin into human soft tissues is lacking.
OBJECTIVES: To investigate the feasibility and plasma PK of subcutaneous dosing 
as well as soft tissue PK of temocillin after intravenous administration to 
healthy volunteers.
METHODS: Eight healthy volunteers received 2 g of temocillin both as intravenous 
and subcutaneous infusion in a randomized two-period crossover study. 
Concentration-time profiles of total temocillin in plasma (after both routes) 
and of unbound temocillin in plasma, muscle and subcutis (only after intravenous 
dosing) were determined up to 12 h post-dose.
RESULTS: Subcutaneous dosing caused some infusion site discomfort but resulted 
in sustained drug concentrations over time with only slightly decreased overall 
exposure compared with intravenous dosing. Plasma protein binding of temocillin 
showed concentration-dependent behaviour and was higher than previously 
reported. Still, unbound drug concentrations in muscle and subcutis determined 
by microdialysis markedly exceeded those in plasma, suggesting good tissue 
penetration of temocillin.
CONCLUSIONS: The subcutaneous administration of temocillin is a valid and 
feasible alternative to intravenous dosing. With the description of plasma 
protein binding and soft tissue PK of temocillin in healthy volunteers, this 
study provides important information that adds to the ongoing characterization 
of the PK profile of temocillin and might serve as input for PK/PD 
considerations.

© The Author(s) 2020. Published by Oxford University Press on behalf of the 
British Society for Antimicrobial Chemotherapy. All rights reserved. For 
permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/jac/dkaa176
PMID: 32433753